Affinage

CITED2

Cbp/p300-interacting transactivator 2 · UniProt Q99967

Length
270 aa
Mass
28.5 kDa
Annotated
2026-06-09
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CITED2 is a nuclear, intrinsically disordered transcriptional co-regulator that operates principally by competing for the CH1/TAZ1 domain of the coactivators CBP/p300, thereby reprogramming which transcription factors gain access to p300's acetyltransferase activity (PMID:14594809, PMID:12778114). Its transactivation domain folds upon binding the zinc-containing CH1 scaffold through an 'LPXL' hot spot that overlaps the HIF-1α binding surface, allowing CITED2 to displace HIF-1α from p300 and act as a negative-feedback brake on hypoxic gene expression — a loop induced by FOXO3a and HIF-1 itself, and that limits both C-terminal and N-terminal HIF-1α transactivation domain activity (PMID:14594809, PMID:12778114, PMID:12149478, PMID:18158893, PMID:21925214). Conversely, CITED2 bridges p300/CBP to a broad set of sequence-specific factors to activate transcription, most prominently the TFAP2 family, with which it forms a trimeric p300–CITED2–TFAP2 complex requiring p300 HAT activity (PMID:11694877, PMID:12586840); it likewise co-activates HNF4α, PPARα/γ, Smad2/3, and ISL1 and occupies target promoters including Pitx2c, Vegfa, Cebpa, Oct4, and Nanog (PMID:15475956, PMID:15051727, PMID:16619037, PMID:17932483, PMID:22504313, PMID:18358466, PMID:27818139, PMID:25377420). Through these activities CITED2 controls left-right body-axis establishment via a BMP-counteracting Nodal→Pitx2c pathway (PMID:15475956, PMID:21224256), adrenal and gonadal specification via the WT1/SF1 axis (PMID:17537799, PMID:19457926), fetal and adult hematopoietic stem cell maintenance upstream of the Ink4a/ARF–p53 axis and GATA2/MCL-1/PTEN (PMID:17644732, PMID:19951693, PMID:14560011, PMID:34715054), hepatic gluconeogenesis by modulating the GCN5 acetyltransferase substrate switch on PGC-1α (PMID:22426420, PMID:27874008), and inflammatory signalling in macrophages by restraining HIF-1α- and STAT1-IRF1-driven proinflammatory programs (PMID:29203644, PMID:34365659). CITED2 abundance and activity are tuned by post-translational control, including FBXL5-directed proteasomal degradation and MAPK1 phosphorylation at T166 in the SRJ domain that enhances TFAP2 coactivation (PMID:25956243, PMID:23082118). Loss-of-function mouse and rat models tie these molecular roles to cardiac, neural crest, hematopoietic, and placental developmental defects (PMID:11694877, PMID:22504313, PMID:36626551).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Established the first defined molecular partner and developmental role for CITED2 by showing it co-activates the TFAP2 transcription factor family, framing it as a transcriptional coactivator rather than an orphan protein.

    Evidence Co-IP, transactivation rescue in Cited2-null fibroblasts, and Cited2 null mouse phenotyping

    PMID:11694877

    Open questions at the time
    • Did not resolve how CITED2 bridges TFAP2 to the general transcription machinery
    • Mechanism connecting molecular defect to the diverse null phenotypes unaddressed
  2. 2002 High

    Defined CITED2's signature activity as a negative regulator of HIF-1α, explaining how it dampens hypoxic gene expression in vivo.

    Evidence Cited2 null mice with qRT-PCR of HIF-1α target genes in hearts and fibroblasts under hypoxia

    PMID:12149478

    Open questions at the time
    • Structural basis of HIF-1α displacement not yet shown
    • Whether inhibition extends beyond C-terminal HIF-1α transactivation unknown
  3. 2003 High

    Solved the structural mechanism of competition, showing the disordered CITED2 TAD folds on the p300/CBP CH1 domain and outcompetes HIF-1α at an overlapping LPXL hot spot.

    Evidence NMR solution structures of the CITED2 TAD–CH1/TAZ1 complex, competitive binding assays, and LPEL mutagenesis with in vivo p300 binding

    PMID:12778114 PMID:14594809

    Open questions at the time
    • Did not address how CITED2 selectively recruits versus displaces partners at the same surface
    • Affinity differences across the many CITED2-CBP-dependent factors not quantified
  4. 2003 High

    Showed CITED2 nucleates a trimeric p300–CITED2–TFAP2 complex whose coactivation depends on p300 HAT activity, and extended the displacement principle to Ets-1, linking CITED2 to MMP suppression under mechanical/TGF-β cues.

    Evidence Co-IP, mammalian two-hybrid, reporter assays with a HAT-deficient p300 mutant, and competitive p300-binding assays in chondrocytes

    PMID:12586840 PMID:12960175

    Open questions at the time
    • Acetylation substrates relevant to TFAP2 targets not identified
    • Generality of Ets-1 displacement across cell types untested
  5. 2003 High

    Placed CITED2 upstream of a polycomb–INK4a/ARF axis controlling proliferation, establishing a developmentally relevant growth-control pathway.

    Evidence Cited2-null MEFs with INK4a/ARF genetic rescue and retroviral Bmi1/Mel18 complementation

    PMID:14560011

    Open questions at the time
    • Direct transcriptional targets linking CITED2 to Bmi1/Mel18 not defined
    • Whether effect is p300-dependent unaddressed
  6. 2004 High

    Connected CITED2 to body-axis patterning through a Nodal→Pitx2c pathway acting with TFAP2 at the Pitx2c promoter.

    Evidence ChIP from embryonic hearts, transient reporter assays, and Cited2-null gene expression analysis

    PMID:15475956

    Open questions at the time
    • How CITED2 initiates left-sided Nodal expression not resolved
    • Cardiac versus extra-cardiac origin of defects unclear at this stage
  7. 2004 Medium

    Broadened the coactivator repertoire to nuclear receptors by demonstrating direct, ligand-dependent coactivation of PPARα and PPARγ.

    Evidence Interaction cloning, GST pull-down, reporter assays, and overexpression/knockdown in hepatocytes

    PMID:15051727

    Open questions at the time
    • Single-lab finding without structural confirmation
    • PPAR target genes in vivo not defined here
  8. 2006 Medium

    Identified CITED2 as a Smad2/3 partner and showed it is itself post-transcriptionally downregulated by TGF-β, defining a regulated CITED2-TGF-β node controlling MMP9 and invasion.

    Evidence Co-IP, two-hybrid, GST pull-down, ChIP at MMP9, knockdown invasion assays, and transcript turnover analysis

    PMID:16619037 PMID:16675452

    Open questions at the time
    • RNA-binding factor mediating TGF-β-driven mRNA destabilization unidentified
    • Reconciliation of CITED2 promoting MMP9 here yet suppressing MMP-1/13 elsewhere unaddressed
  9. 2007 High

    Established CITED2 within feedback and developmental gene circuits: a FOXO3a/HIF-1-induced antiapoptotic feedback loop, a coactivator of HNF4α for fetal liver, a WT1/SF1-pathway component for adrenal specification, and a requirement for fetal liver hematopoiesis.

    Evidence Reporter and knockdown assays under hypoxia; Co-IP and ChIP in null livers; mouse genetic epistasis; transplantation assays

    PMID:17537799 PMID:17644732 PMID:17932483 PMID:18158893

    Open questions at the time
    • Whether these roles share the common p300-bridging mechanism not directly tested across contexts
    • Direct CITED2 targets in hematopoietic progenitors not yet defined
  10. 2009 High

    Defined a cell-autonomous requirement for CITED2 in adult HSC maintenance acting upstream of the Ink4a/ARF–p53 axis, and extended the WT1/SF1 pathway to Sry-dependent testis determination.

    Evidence Conditional knockout with Ink4a/Arf and Trp53 epistasis and transplantation; multi-allele genetic epistasis with Wt1/Sf1/Sry

    PMID:19457926 PMID:19951693

    Open questions at the time
    • Direct transcriptional link between CITED2 and Ink4a/Arf repression not shown
    • Molecular mechanism setting Sry expression threshold unresolved
  11. 2010 Medium

    Generalized the p300-displacement mechanism to NF-κB p65 and resolved that CITED2 cardiac defects arise extra-cardiacally from failed left-right axis establishment, with CITED2 acting as a BMP potentiator.

    Evidence Co-IP and p65 acetylation/ChIP assays in macrophages; lineage-specific conditional knockouts with BMP epistasis

    PMID:21098220 PMID:21224256

    Open questions at the time
    • In vivo NF-κB targets restrained by CITED2 not yet mapped
    • Mechanistic link between BMP potentiation and Nodal suppression incomplete
  12. 2011 Medium

    Expanded HIF inhibition to the N-terminal transactivation domain and revealed that CITED2 levels also tune p53 acetylation/stability and drug sensitivity through p300.

    Evidence Co-IP domain mapping and reporter assays; shRNA knockdown with p53 acetylation/ubiquitination and cisplatin cytotoxicity assays

    PMID:21660965 PMID:21925214

    Open questions at the time
    • Both single-lab; how CITED2 selectively gates p53 versus HIF access to p300 unclear
    • In vivo relevance of CITED2-p53 axis not established
  13. 2012 High

    Defined a major metabolic role: CITED2 controls hepatic gluconeogenesis by blocking GCN5-mediated PGC-1α acetylation, integrating glucagon/insulin signalling, and directly regulates Vegfa with TFAP2 in the developing heart.

    Evidence Conditional knockout mice, Co-IP, PGC-1α acetylation and glucose-production assays; cardiomyocyte-specific knockout with ChIP and reporter at Vegfa

    PMID:22426420 PMID:22504313

    Open questions at the time
    • How signalling-driven changes in CITED2 abundance are achieved mechanistically not fully resolved
    • Coordination of metabolic versus coactivator roles within the same cell unaddressed
  14. 2012 Medium

    Implicated CITED2 in pluripotency and cell-cycle control, occupying the Oct4 promoter during ESC differentiation and acting as a MYC/p300 versus HDAC1 switch between proliferation and quiescence; also identified it as a PPARγ effector tumor suppressor and a Cdk4→CITED2→PPARγ neuronal apoptosis mediator.

    Evidence ChIP and knockout ESC differentiation; Co-IP of CITED2-p300/HDAC1/MYC with cell-cycle assays; PPARγ ChIP and gain/loss-of-function; neuronal apoptosis assays

    PMID:18495890 PMID:22761414 PMID:22814619 PMID:23212831

    Open questions at the time
    • Context determining pro- versus anti-proliferative outcome not defined
    • All single-lab with limited cross-validation
  15. 2013 Medium

    Linked CITED2 to cellular metabolism by direct promoter regulation of glycolytic genes (HK1) in ESCs and metabolic gene programs (Pdk2/4, LDH) in HSCs, coupling its transcriptional role to glucose handling and ROS control.

    Evidence ChIP and metabolic phenotyping in knockout ESCs and conditional-knockout HSCs with PI3K/Akt inhibition; ERK1/2-dependent mRNA stabilization in renal cells

    PMID:23792300 PMID:24083546 PMID:24265312

    Open questions at the time
    • Whether metabolic gene regulation is direct p300-bridged coactivation untested
    • Single-lab metabolic readouts
  16. 2015 Medium

    Defined an FBXL5-directed proteasomal degradation route controlling CITED2 abundance and HIF-1α access to p300, and placed CITED2/p300 upstream of p53-dependent ERCC1 chromatin remodeling in DNA damage response.

    Evidence Co-IP, RNAi, proteasome-dependent degradation and CITED2-CH1 interaction assays; ChIP of p53 and histone acetylation at ERCC1 with DNA-repair assays

    PMID:25956243 PMID:26384430

    Open questions at the time
    • Degron and ubiquitination sites on CITED2 not mapped
    • Both single-lab without reciprocal validation
  17. 2016 Medium

    Refined regulatory inputs and outputs: established MAPK1 phosphorylation at T166 as a tunable enhancer of TFAP2 coactivation, demonstrated a GCN5 substrate-switch mechanism for gluconeogenesis, and identified CITED2-driven IKKα/NF-κB and CCL20 programs in breast cancer alongside cooperation with ISL1 in cardiogenesis.

    Evidence In vitro kinase assays with T166N mutant; PKA/GCN5 kinase and HAT assays with ChIP; ChIP and rescue/invasion/macrophage-recruitment assays; Co-IP with ISL1 and ESC cardiac differentiation

    PMID:23082118 PMID:27216153 PMID:27818139 PMID:27874008 PMID:29399152

    Open questions at the time
    • T166N knock-in produced no morphological phenotype, leaving physiological importance of this site uncertain
    • Cancer-promoting versus tumor-suppressing roles of CITED2 not reconciled mechanistically
  18. 2018 Medium

    Demonstrated CITED2 restrains macrophage inflammation by limiting HIF-1α stability and promoting PPARγ activity, and identified a chaperone-like role guiding PRMT5/p300 to activate nucleolin in cancer metastasis.

    Evidence Myeloid-specific knockout with Egln3/HIF-1α rescue and sepsis model; Co-IP of CITED2-PRMT5/p300/nucleolin with migration and xenograft assays

    PMID:29203644 PMID:30291252

    Open questions at the time
    • Whether nucleolin chaperone role uses the same CH1-binding surface unknown
    • Direct CITED2 control of HIF-1α prolyl-hydroxylase pathway not fully defined
  19. 2021 High

    Identified additional macrophage and HSC effectors of CITED2, defining a STAT1-IRF1 inflammatory axis and GATA2/MCL-1/PTEN as required HSC targets with in vivo disease relevance.

    Evidence Myeloid conditional knockout with ChIP and IRF1 siRNA rescue plus atherosclerosis model; hematopoietic conditional knockout with MCL-1 transgenic rescue and Pten compound heterozygote epistasis

    PMID:34365659 PMID:34715054

    Open questions at the time
    • Whether GATA2/MCL-1/PTEN are direct CITED2/p300 transcriptional targets not fully shown
    • Integration of metabolic and survival programs in HSCs unresolved
  20. 2023 High

    Extended CITED2's developmental requirement to placentation, identifying it as a conserved regulator of trophoblast invasion and junctional-zone integrity.

    Evidence Cited2 null rat and human trophoblast loss-of-function with localization and invasion/EVT differentiation assays

    PMID:36626551

    Open questions at the time
    • Transcriptional targets driving trophoblast invasion not defined
    • Whether the role depends on HIF competition or TFAP2 coactivation unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CITED2 selects between displacing (HIF-1α, p65, Ets-1) and recruiting (TFAP2, HNF4α, nuclear receptors, ISL1) factors at the same p300/CBP CH1 surface, and what determines its context-specific pro- versus anti-proliferative and pro- versus anti-tumor outcomes, remains unresolved.
  • No unified model reconciling competitive inhibition and coactivation at CH1
  • Cell-type determinants of opposing growth outcomes undefined
  • Quantitative affinity hierarchy among CITED2-CBP-dependent partners not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 1 GO:0005730 nucleolus 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-1430728 Metabolism 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CREBBPEP300FBXL5HIF1AHNF4AISL1SMAD3TFAP2A
Complex memberships
p300/CBP–CITED2–TFAP2 trimeric complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 NMR structure of CITED2 transactivation domain bound to the CBP TAZ1 (CH1) domain reveals that CITED2 TAD is intrinsically disordered and folds upon binding, forming a helix (αA) and extended structure that wraps around TAZ1. CITED2 and HIF-1α share an overlapping 'LP(E/Q)L' binding hot spot on CH1 but use partly non-overlapping surfaces, allowing competitive displacement of HIF-1α by CITED2. NMR structure determination of CITED2 TAD-CBP TAZ1 complex; competitive binding assays The Journal of biological chemistry High 14594809
2003 High-resolution solution structure of the CITED2 TAD bound to the p300/CBP CH1 domain shows CITED2 TAD folds on the helical Zn2+-containing CH1 scaffold and disrupts the HIF-1α C-TAD–CH1 complex by binding CH1 with higher affinity via an overlapping 'LPXL' motif. Mutation of the LPEL sequence in full-length CITED2 abolishes p300 binding in vivo. High-resolution NMR solution structure; in vitro competition binding; LPEL mutagenesis with in vivo p300-binding assay Nature structural biology High 12778114
2001 CITED2 physically interacts with and co-activates all isoforms of transcription factor AP-2 (TFAP2A/B/C). Transactivation by TFAP2 isoforms is defective in Cited2−/− mouse embryonic fibroblasts and is rescued by ectopic CITED2. Loss of Cited2 causes cardiac malformations, adrenal agenesis, neural crest defects, and exencephaly in mice. Co-immunoprecipitation; rescue transactivation assay in knockout fibroblasts; Cited2 null mouse phenotyping Nature genetics High 11694877
2003 p300/CBP, CITED2, and TFAP2A form a trimeric complex in vivo (co-IP from transfected cells). CITED2 interacts with the dimerization domain of TFAP2C (conserved in TFAP2A/B). Full-length p300 interacts with TFAP2A only when CITED2 is co-transfected (mammalian two-hybrid). A HAT-deficient p300 mutant (D1399Y) fails to co-activate TFAP2A and fails to interact with TFAP2A, indicating that HAT activity of p300 is required for TFAP2A co-activation. Co-immunoprecipitation from transfected U2-OS cells; mammalian two-hybrid; reporter co-activation assay with p300 HAT mutant The Journal of biological chemistry High 12586840
2002 Cited2 functions as a negative regulator of HIF-1α transcriptional activity in vivo: Cited2−/− embryonic hearts show elevated mRNA levels of HIF-1α-responsive genes (VEGF, Glut1, PGK1), and Cited2−/− fibroblasts display enhanced expression of HIF-1α-responsive genes under hypoxia, consistent with competitive inhibition of HIF-1α binding to CBP/p300. Cited2 null mouse model; quantitative RT-PCR of HIF-1α target genes in knockout hearts and fibroblasts under hypoxia Proceedings of the National Academy of Sciences of the United States of America High 12149478
2004 CITED2 controls left-right patterning through a Nodal→Pitx2c pathway. CITED2 and TFAP2 proteins are detected at the Pitx2c promoter in embryonic hearts (ChIP), and they activate Pitx2c transcription in transient transfection assays. Cited2−/− mice lack Nodal, Pitx2c, and Ebaf expression in the left lateral plate mesoderm. Chromatin immunoprecipitation (ChIP) from embryonic hearts; transient transfection reporter assays; Cited2 null mouse gene expression analysis Nature genetics High 15475956
2007 FOXO3a induces CITED2 transcription during hypoxia in an HIF-1-dependent manner. CITED2, in turn, functions in a negative feedback loop to reduce HIF-1 activity, resulting in reduced expression of proapoptotic HIF-1 target genes NIX and RTP801, thereby inhibiting HIF-1-induced apoptosis. Transcriptional reporter assays; siRNA knockdown of FOXO3a and CITED2; measurement of HIF-1 target gene expression in fibroblasts and breast cancer cells under hypoxia Molecular cell Medium 18158893
2007 Cited2 interacts with WT1 to stimulate expression of SF-1 (Nr5a1) in the adrenogonadal primordium (AGP) above the threshold required for adrenal cortex specification. Genetic reduction of Cited2 or Wt1 dosage proportionally reduces SF-1 levels in the AGP and impairs adrenal development; Sf-1/Cited2 double heterozygotes confirm they act in the same pathway. Mouse genetic epistasis (double heterozygotes, compound mutants); gene expression analysis (immunostaining, qPCR) Development (Cambridge, England) High 17537799
2004 CITED2 is a coactivator of PPARα: it interacts directly with PPARα predominantly via the ligand-binding domain (identified by interaction cloning), acts as a dose-dependent transcriptional coactivator of PPARα-dependent reporter genes in the presence of ligands, and also coactivates PPARγ but not PPARβ. cDNA library interaction cloning with bacterially expressed PPARα; GST pull-down; transient transfection reporter assays; stable overexpression/siRNA knockdown in hepatocytes The Journal of biological chemistry Medium 15051727
2003 CITED2 is upregulated by flow shear (5 dyn/cm²) in human chondrocytes and downregulates MMP-1 and MMP-13 mRNA and enzyme activity. CITED2 associates with p300, displacing Ets-1 from p300, thereby suppressing Ets-1-dependent MMP transcription. TGF-β stimulation promotes both CITED2 expression and its association with p300. Sense/antisense CITED2 overexpression under flow shear; co-immunoprecipitation of CITED2-p300 and p300-Ets-1 complexes; MMP activity assays The Journal of biological chemistry Medium 12960175
2006 CITED2 physically interacts with Smad2 and Smad3 (co-IP, mammalian two-hybrid, GST pull-down). p300 enhances the CITED2–Smad3 interaction and transcriptional responses. CITED2 is recruited to the MMP9 promoter upon TGF-β stimulation (ChIP). CITED2 enhances TGF-β-mediated MMP9 upregulation and knockdown of CITED2 attenuates TGF-β-induced MMP9 expression and cell invasion. Co-immunoprecipitation; mammalian two-hybrid; GST pull-down; chromatin immunoprecipitation; siRNA knockdown; invasion assay Oncogene High 16619037
2012 CITED2 is required for hepatic gluconeogenesis: it inhibits acetylation of PGC-1α by blocking its interaction with the acetyltransferase GCN5, reducing PGC-1α acetylation and increasing its coactivation of gluconeogenic genes. Glucagon-cAMP-PKA signaling increases hepatic CITED2 abundance; insulin–PI3K–Akt signaling disrupts the CITED2–GCN5 interaction. Loss of hepatic CITED2 suppresses gluconeogenesis in diabetic mice. Conditional knockout mice; co-immunoprecipitation (CITED2-GCN5 interaction); PGC-1α acetylation assay; gluconeogenic gene expression analysis; in vivo glucose production assays Nature medicine High 22426420
2016 During fasting, PKA phosphorylates GCN5 in a CITED2-dependent manner, increasing GCN5 histone acetyltransferase activity while attenuating its activity toward PGC-1α. This CITED2-dependent substrate switch of GCN5 simultaneously promotes epigenetic activation of gluconeogenic gene promoters and PGC-1α-mediated coactivation, thereby triggering gluconeogenesis. In vitro kinase assay (PKA phosphorylation of GCN5); histone acetyltransferase activity assay; ChIP; gluconeogenic gene expression in CITED2-deficient mice Nature communications High 27874008
2007 CITED2 is required for normal fetal liver hematopoiesis: Cited2−/− fetal liver shows reduced Lin−c-Kit+Sca-1+ cells and progenitors of all lineages, severely impaired colony formation, and compromised primary and secondary transplantation reconstitution of T, B, and myeloid lineages. Cited2 null mouse model; flow cytometry; colony-forming assay; competitive bone marrow transplantation Blood High 17644732
2009 Cited2 is selectively and cell-autonomously required for adult hematopoietic stem cell (HSC) maintenance. Conditional deletion of Cited2 causes loss of HSCs and multilineage bone marrow failure. Additional deletion of Ink4a/Arf or Trp53 (p53) restores HSC functionality and rescues mice from bone marrow failure, placing Cited2 upstream of the Ink4a/Arf–p53 axis in HSC maintenance. Conditional knockout (Mx1-Cre); bone marrow transplantation; genetic epistasis with Ink4a/Arf and Trp53 null alleles; flow cytometry Cell stem cell High 19951693
2012 HIF-1α deletion partially rescues impaired HSC quiescence and reconstitution capacity caused by Cited2 deficiency, and restores expression of p57 and Hes1 but not Egr1, indicating that CITED2 regulates HSC quiescence through both HIF-1-dependent and HIF-1-independent pathways. Double-conditional knockout (Cited2 and HIF-1α); bone marrow transplantation; flow cytometry; transcriptional profiling Blood High 22308296
2003 Cited2 controls fibroblast proliferation via the polycomb-group genes Bmi1 and Mel18: Cited2−/− fibroblasts show premature proliferative arrest with increased p16INK4a, p19ARF, and p15INK4b expression and reduced Bmi1/Mel18 levels. Deletion of INK4a/ARF completely rescues proliferative defects of Cited2−/− fibroblasts. Bmi1 and Mel18 retroviruses also rescue proliferation, placing them downstream of Cited2. Cited2 null mouse embryonic fibroblasts; INK4a/ARF genetic rescue; retroviral complementation with CITED2, Bmi1, Mel18 Molecular and cellular biology High 14560011
2007 Cited2 is a coactivator of HNF4α and is essential for fetal liver development. CITED2 physically interacts with HNF4α and is recruited to HNF4α-responsive promoters (ChIP). In the absence of Cited2, HNF4α binding to its target gene promoters is reduced. Cited2 null mouse fetal liver; co-immunoprecipitation (CITED2–HNF4α); chromatin immunoprecipitation The EMBO journal High 17932483
2011 CITED2 attenuates hypoxic activation of HIF-1α N-terminal transactivation domain (NAD)-dependent genes in addition to C-terminal TAD (CAD)-dependent genes. NAD interacts with both CH1 and CH3 domains of p300; CITED2 blocks NAD binding to CH1 but not CH3. pVHL also inhibits NAD activity by blocking the p300-NAD interaction. Co-immunoprecipitation (NAD-CH1, NAD-CH3 interactions); reporter gene assays for NAD- and CAD-dependent targets; siRNA knockdown Biochimica et biophysica acta Medium 21925214
2010 CITED2 constitutively localizes in the nucleus and interacts with p300, preventing p65 (NF-κB) from binding to p300, impairing p65 acetylation and p65 binding to target promoters. LPS induces CITED2 expression via NF-κB in macrophages, establishing a negative feedback loop. CITED2 also sensitizes cells to TNF-α-induced apoptosis. Subcellular fractionation/nuclear localization imaging; co-immunoprecipitation (CITED2-p300, p65-p300); p65 acetylation assay; ChIP; ectopic expression and knockdown reporter assays Journal of immunology Medium 21098220
2007 CITED2 is degraded via the ubiquitin-proteasome system and is stabilized by proteasome inhibitors. Stabilized CITED2 inhibits HIF-1α C-terminal transactivation domain (CAD) activity and blocks p300 recruitment by HIF-1α, explaining the paradoxical reduction of HIF-1α transcriptional activity upon proteasome inhibition. Proteasome inhibitor treatment (MG132); CITED2 siRNA rescue; co-immunoprecipitation (HIF-1α-p300); reporter assays Oncogene Medium 17906695
2006 TGF-β downregulates CITED2 mRNA post-transcriptionally via the Smad pathway (requires Smad4, blocked by Smad7 overexpression), accelerating turnover of Cited2 transcripts. The C-terminal conserved coding region of Cited2 is required for TGF-β-mediated mRNA destabilization. Transcriptional rate is not affected. Nuclear run-on analysis; promoter reporter assay; Smad7 overexpression/Smad4 knockdown; transcript turnover assay with transcription inhibitors; heterologous promoter-driven Cited2 coding sequence constructs The Journal of biological chemistry Medium 16675452
2009 CITED2 acts within the WT1/SF1 regulatory pathway in the gonad to increase Sry expression above the threshold required for testis determination. Reducing Wt1 or Sf1 gene dosage in Cited2 mutants produces partial XY sex reversal, and a hypomorphic SryPOS allele causes full sex reversal, placing Sry as a downstream target of the CITED2/WT1/SF1 pathway. Genetic epistasis in mice (Cited2, Wt1, Sf1 compound mutants; SryPOS allele); gene expression analysis of Sry and Sf1 during sex determination Human molecular genetics High 19457926
2010 Loss of Cited2 from heart progenitors (Nkx2-5-Cre) does not alter cardiac development, whereas extra-cardiac deletion establishes that heart defects in Cited2-null embryos arise from failure to establish the left-right body axis. Cited2 is identified as a potentiator of BMP signalling that counteracts initiation of Nodal expression in the left lateral plate mesoderm. Conditional knockout (multiple Cre drivers); epistasis with BMP signaling pathway; gene expression analysis in node and LPM Human molecular genetics High 21224256
2012 CITED2 functions as a molecular switch between TGF-α-induced proliferation and TGF-β-mediated quiescence: upon TGF-α induction, CITED2 is induced by MYC and recruits p300 to promote MYC-p300-mediated transactivation of E2F3, driving G1/S progression. CITED2 also interacts with HDAC1 and potentiates MYC-HDAC1-mediated suppression of p21CIP1. TGF-β downregulates CITED2, abolishing these effects. Co-immunoprecipitation (CITED2-p300, CITED2-HDAC1, MYC-HDAC1 complexes); reporter assays; siRNA knockdown; overexpression; cell cycle analysis Cell death and differentiation Medium 22814619
2008 CITED2 acts as a coactivator of liver-enriched transcription factor HNF4α for fetal liver development; in neurons, CITED2 is upregulated by DNA damage downstream of Cdk4 and activates PPARγ, which is required for DNA damage-induced neuronal apoptosis. CITED2 overexpression promotes death and CITED2 deficiency protects; Cdk4 blockade prevents CITED2 induction. Gene array plus RT-PCR/Western blot in camptothecin-treated neurons; CITED2 overexpression/knockdown with apoptosis assay; Cdk4 inhibitor; PPARγ reporter assay The Journal of neuroscience Medium 18495890
2012 CITED2 is recruited to the Oct4 promoter during early embryonic stem cell differentiation (ChIP) and regulates Oct4 expression. Loss of Cited2 delays silencing of pluripotency genes (Oct4, Klf4, Sox2, c-Myc) and impairs cardiomyocyte, hematopoietic, and neuronal differentiation. Cited2 knockout ESCs; chromatin immunoprecipitation (CITED2 at Oct4 promoter); differentiation assays; gene expression analysis The Journal of biological chemistry Medium 22761414
2012 CITED2 is a direct effector of PPARγ in hepatocellular carcinoma: PPARγ activation induces CITED2 expression and is the most prominent PPARγ-bound target gene by ChIP-PCR. CITED2 knockdown increases cell viability and promotes G1-S transition, while ectopic CITED2 suppresses HCC cell growth associated with upregulation of CDK inhibitors and tumor suppressor genes. Chromatin immunoprecipitation (PPARγ at CITED2 promoter); loss- and gain-of-function assays; cell cycle analysis Cancer Medium 23212831
2015 FBXL5 directly interacts with CITED2 and targets it for proteasomal degradation. Depletion of FBXL5 by RNAi increases CITED2 protein levels; overexpression of FBXL5 decreases CITED2 levels in a proteasome-dependent manner, impairs CITED2–CH1(p300) interaction, and enables HIF-1α N-terminal transactivation domain activity. Co-immunoprecipitation (CITED2-FBXL5); RNAi knockdown of FBXL5; proteasome inhibitor rescue; CITED2-CH1 interaction assay in living cells; HIF-1α TAD reporter assay Archives of biochemistry and biophysics Medium 25956243
2010 Moderate mechanical loading (2.5 MPa, 1 Hz intermittent hydrostatic pressure) upregulates CITED2 in chondrocytes via p38δ phosphorylation. CITED2 suppresses MMP-1 expression by competing with Ets-1 for binding to p300 (demonstrated by competitive binding and transcription assays). In vivo, daily passive joint motion prevents MMP-1 upregulation and cartilage degradation coincident with CITED2 induction. Competitive binding assay (CITED2 vs Ets-1 for p300); transcription assays; in vitro hydrostatic pressure system; in vivo hind-limb immobilization model; p38δ-specific inhibition/phosphorylation analysis FASEB journal Medium 20826544
2008 In nucleus pulposus cells, HIF-2α preferentially regulates CITED2 expression and promoter activity under hypoxia (unlike HIF-1α's predominant role in most other tissues). Forced expression or suppression of CITED2 causes corresponding changes in VEGF expression, establishing CITED2 as a regulator of VEGF in this cell type. HIF-2α/HIF-1α siRNA suppression; gain- and loss-of-function CITED2 constructs; promoter activity assays; VEGF expression measurement Arthritis and rheumatism Medium 19035510
2011 CITED2 knockdown induces CBP/p300-mediated p53 acetylation at Lys373, decreases p53 ubiquitination, and stabilizes p53 protein, sensitizing cancer cells to cisplatin-induced apoptosis in a p53-dependent manner. shRNA knockdown; p53 acetylation assay (Lys373); p53 ubiquitination assay; cisplatin cytotoxicity in p53-positive vs p53-defective cell lines Journal of cellular physiology Medium 21660965
2015 CITED2 silencing reduces ERCC1 expression and impairs p53-dependent chromatin relaxation (H3K9Ac, H3K14Ac) at the ERCC1 promoter in response to cisplatin. ChIP shows p53 and acetylated histones bind the ERCC1 promoter upon cisplatin treatment in a CITED2/p300-dependent manner, establishing a CITED2/p300/p53/ERCC1 pathway in DNA damage response. shRNA knockdown; chromatin immunoprecipitation (p53, H3K9Ac, H3K14Ac at ERCC1 promoter); ERCC1 reporter; DNA damage comet assay; xenograft model Nucleic acids research Medium 26384430
2012 CITED2 cardiomyocyte-specific knockout (Cited2Nkx) causes ventricular septal defects and compact layer thinning associated with reduced capillary density and 1.5-fold reduction in Vegfa expression. ChIP confirms CITED2 occupancy at the Vegfa promoter in mouse embryonic hearts; CITED2 activates human VEGFA promoter cooperatively with TFAP2 in transient transfection assays. Cardiomyocyte-specific conditional knockout; histology and MRI; chromatin immunoprecipitation (CITED2 at Vegfa promoter); transient transfection reporter assay European heart journal High 22504313
2008 Cited2 and Tcfap2c complex is present at the Cebpa promoter in E18.5 lungs (ChIP) and activates Cebpa transcription. Loss of Cited2 reduces Cebpa expression in fetal lungs and impairs alveolar epithelial cell differentiation. Cited2 null mouse lung; chromatin immunoprecipitation (Cited2, Tcfap2c at Cebpa promoter); gene expression analysis Developmental biology Medium 18358466
2018 CITED2 acts as a molecular chaperone guiding PRMT5 and p300 to nucleolin, thereby activating nucleolin. The CITED2-nucleolin axis stimulates cell migration through epithelial-mesenchymal transition and promotes prostate cancer metastasis in a xenograft model. Co-immunoprecipitation (CITED2-PRMT5, CITED2-p300, CITED2-nucleolin); functional migration/invasion assays; xenograft mouse model Nature communications Medium 30291252
2018 CITED2 deficiency in macrophages elevates HIF-1α protein stability and proinflammatory cytokine/chemokine gene expression; overexpression of Egln3 (a prolyl hydroxylase) or HIF-1α inhibition completely reverses elevated proinflammatory gene expression in Cited2-deficient macrophages. CITED2 also promotes PPARγ activation and anti-inflammatory gene expression. Myeloid-specific conditional knockout; Egln3 overexpression rescue; HIF-1α inhibition rescue; gain- and loss-of-function reporter assays; endotoxin sepsis model Molecular and cellular biology High 29203644
2021 CITED2 deficiency in macrophages elevates STAT1 transcriptional activity and IRF1 expression; siRNA-mediated knockdown of IRF1 completely reverses elevated proinflammatory gene expression in CITED2-deficient macrophages. Myeloid-CITED2-deficient mice on Apoe−/− background develop larger atherosclerotic lesions. Myeloid-specific conditional knockout; ChIP (STAT1 enrichment on IRF1 promoter); IRF1 siRNA rescue; atherosclerosis lesion quantification FASEB journal High 34365659
2016 CITED2 is recruited to the IKKα promoter in breast cancer cells (ChIP), directly regulating IKKα expression. CITED2 knockdown reduces IKKα and several NF-κB target genes; restoration of IKKα rescues the invasive ability lost upon CITED2 knockdown, demonstrating a CITED2→IKKα→NF-κB axis in breast cancer metastasis. Chromatin immunoprecipitation (CITED2 at IKKα promoter); shRNA knockdown; IKKα rescue experiment; invasion assay; xenograft model Molecular cancer research Medium 27216153
2016 CITED2 is recruited to the CCL20 promoter in MDA-MB-231 breast cancer cells (ChIP), and CITED2 knockdown reduces CCL20 expression and attenuates macrophage recruitment both in vitro and in orthotopic tumors. Chromatin immunoprecipitation (CITED2 at CCL20 promoter); shRNA knockdown; Transwell macrophage recruitment assay; orthotopic xenograft Oncology letters Medium 29399152
2016 CITED2 cooperates physically with ISL1 (co-immunoprecipitation) and together they promote cardiomyocyte differentiation from mouse ESCs. Loss of Cited2 impairs early mesoderm and cardiogenic transcription factor expression (Isl1, Gata4, Tbx5); CITED2 recombinant protein rescues cardiogenic defects in Cited2-depleted cells. Co-immunoprecipitation (CITED2-ISL1); Cited2 knockdown in ESC differentiation; recombinant protein rescue; cardiac differentiation assay Stem cell reports Medium 27818139
2015 Cited2 directly targets Nanog, Tbx3, and Klf4 in mouse ESCs and is required for their expression; constitutive Nanog expression partially rescues the proliferation, survival, and self-renewal defects caused by Cited2 depletion, positioning Nanog downstream of Cited2 in the pluripotency network. Acute Cited2 deletion in ESCs; ChIP (CITED2 at Nanog/Tbx3/Klf4 loci); Nanog overexpression rescue; self-renewal assay Stem cells (Dayton, Ohio) Medium 25377420
2013 Cited2 is recruited to the hexokinase 1 (HK1) gene promoter (ChIP) in mouse ESCs to regulate HK1 transcription, coordinating glucose metabolism. Cited2 knockout ESCs show enhanced glycolysis, reduced glucose oxidation, abnormal mitochondrial morphology, and decreased ATP, correlated with defective differentiation under hypoxia. Cited2 knockout ESCs; chromatin immunoprecipitation (CITED2 at HK1 promoter); metabolic assays (glycolysis, oxygen consumption, ATP); differentiation assay under hypoxia The Journal of biological chemistry Medium 24265312
2013 Cited2 deficiency in adult HSCs reduces expression of Pdk2, Pdk4, LDHB, and LDHD, leading to decreased glycolysis, elevated reactive oxygen species, and increased mitochondrial activity. Inhibition of PI3K/Akt (but not mTORC1) partially restores Pdk4 expression in Cited2-deficient HSCs. Conditional knockout HSCs; metabolic assays (glycolysis, mitochondrial activity, ROS); PI3K/Akt and mTORC1 inhibitors; gene expression analysis Stem cells and development Medium 24083546
2013 Indoxyl sulfate upregulates CITED2 through post-transcriptional mRNA stabilization involving the ERK1/2 pathway (not HIF-1α protein level changes), thereby functionally impairing HIF-1α C-terminal transactivation domain activity and suppressing HIF-1 target genes. mRNA stability assay; ERK1/2 pathway inhibition; HIF-1α CTAD reporter; protein and mRNA quantification in HK-2 cells FASEB journal Medium 23792300
2012 CITED2 is phosphorylated by MAPK1 (ERK2) in vitro at T166 within the SRJ domain. MAPK1 activation enhances the TFAP2 coactivation function of CITED2 but not of the T166N mutant, establishing T166 as a regulatory phosphorylation site for CITED2 coactivation activity. In vitro kinase assay (MAPK1 phosphorylation of CITED2); T166N point mutation; TFAP2 coactivation reporter assay; knock-in mouse (no morphological phenotype with T166N or ΔSRJ alleles) PloS one Medium 23082118
2021 CITED2 is required for expression of key HSC regulators GATA2, MCL-1, and PTEN. Hematopoietic-specific MCL-1 overexpression partially rescues the Cited2-deficient HSC pool and reconstitution potential. Cited2;Pten compound heterozygotes show decreased HSC numbers and failed reconstitution, placing PTEN downstream of CITED2. Hematopoietic-specific conditional knockout; MCL-1 transgenic rescue; Cited2;Pten compound heterozygotes; bone marrow transplantation; transcriptomics/GSEA Stem cell reports High 34715054
2023 CITED2 is distinctively expressed in junctional zone and invasive trophoblast cells in rat placenta and in extravillous trophoblast (EVT) cell columns in human placenta. Homozygous Cited2 deletion disrupts the junctional zone, delays intrauterine trophoblast invasion, and compromises trophoblast plasticity, establishing CITED2 as a conserved regulator of deep hemochorial placentation. Cited2 null rat and human trophoblast loss-of-function; immunofluorescence localization; trophoblast invasion assays; EVT lineage differentiation assays Proceedings of the National Academy of Sciences of the United States of America High 36626551

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator. Nature genetics 282 11694877
2007 FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2. Molecular cell 237 18158893
2002 The essential role of Cited2, a negative regulator for HIF-1alpha, in heart development and neurulation. Proceedings of the National Academy of Sciences of the United States of America 179 12149478
2003 Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2. Nature structural biology 176 12778114
2004 Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway. Nature genetics 175 15475956
2003 Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. The Journal of biological chemistry 132 12586840
2002 Folic acid prevents exencephaly in Cited2 deficient mice. Human molecular genetics 132 11823447
2005 Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development. Development (Cambridge, England) 114 15750185
2003 CITED2-mediated regulation of MMP-1 and MMP-13 in human chondrocytes under flow shear. The Journal of biological chemistry 111 12960175
2007 Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development (Cambridge, England) 104 17537799
2005 Identification and functional analysis of CITED2 mutations in patients with congenital heart defects. Human mutation 104 16287139
2004 Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated receptor alpha coregulator. The Journal of biological chemistry 101 15051727
2003 Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites. The Journal of biological chemistry 97 14594809
2006 Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta. Developmental biology 94 16579983
2006 Cited2 modulates TGF-beta-mediated upregulation of MMP9. Oncogene 93 16619037
2009 Cited2 is an essential regulator of adult hematopoietic stem cells. Cell stem cell 91 19951693
2007 Cited1 and Cited2 are differentially expressed in the developing kidney but are not required for nephrogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 78 17615577
2003 Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF. Molecular and cellular biology 77 14560011
2010 Physiological loading of joints prevents cartilage degradation through CITED2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 74 20826544
2012 CITED2 links hormonal signaling to PGC-1α acetylation in the regulation of gluconeogenesis. Nature medicine 66 22426420
2007 Cited2, a coactivator of HNF4alpha, is essential for liver development. The EMBO journal 66 17932483
2012 CITED2 functions as a molecular switch of cytokine-induced proliferation and quiescence. Cell death and differentiation 65 22814619
2008 Cited2 modulates hypoxia-inducible factor-dependent expression of vascular endothelial growth factor in nucleus pulposus cells of the rat intervertebral disc. Arthritis and rheumatism 64 19035510
2018 Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway. Nature communications 63 30291252
2010 Negative feedback regulation of NF-κB action by CITED2 in the nucleus. Journal of immunology (Baltimore, Md. : 1950) 62 21098220
2015 MicroRNAs in the Myocyte Enhancer Factor 2 (MEF2)-regulated Gtl2-Dio3 Noncoding RNA Locus Promote Cardiomyocyte Proliferation by Targeting the Transcriptional Coactivator Cited2. The Journal of biological chemistry 55 26240138
2012 HIF-1α deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency. Blood 53 22308296
2010 Loss of Cited2 causes congenital heart disease by perturbing left-right patterning of the body axis. Human molecular genetics 53 21224256
2006 Partial rescue of defects in Cited2-deficient embryos by HIF-1alpha heterozygosity. Developmental biology 50 17022961
2007 Cited2 is required for normal hematopoiesis in the murine fetal liver. Blood 49 17644732
2007 A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion. FEBS letters 49 18054336
2008 Cited2 is required for fetal lung maturation. Developmental biology 48 18358466
2008 Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis. Development (Cambridge, England) 47 18653562
1999 Molecular cloning and chromosomal localization of the human CITED2 gene encoding p35srj/Mrg1. Genomics 47 10552932
2009 The transcription co-factor CITED2 functions during sex determination and early gonad development. Human molecular genetics 46 19457926
2012 Pan-histone deacetylase inhibitor panobinostat sensitizes gastric cancer cells to anthracyclines via induction of CITED2. Gastroenterology 45 22465428
2014 Cited2 is required in trophoblasts for correct placental capillary patterning. Developmental biology 44 24803182
2013 Indoxyl sulfate signals for rapid mRNA stabilization of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) and suppresses the expression of hypoxia-inducible genes in experimental CKD and uremia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 42 23792300
2018 CITED2 Restrains Proinflammatory Macrophage Activation and Response. Molecular and cellular biology 39 29203644
2015 High Glucose-Repressed CITED2 Expression Through miR-200b Triggers the Unfolded Protein Response and Endoplasmic Reticulum Stress. Diabetes 39 26450995
2014 CITED2 mutation and methylation in children with congenital heart disease. Journal of biomedical science 39 24456003
2011 Knockdown of CITED2 using short-hairpin RNA sensitizes cancer cells to cisplatin through stabilization of p53 and enhancement of p53-dependent apoptosis. Journal of cellular physiology 38 21660965
2010 Gonadal defects in Cited2-mutant mice indicate a role for SF1 in both testis and ovary differentiation. The International journal of developmental biology 37 19757380
2020 Diabetes-induced glucolipotoxicity impairs wound healing ability of adipose-derived stem cells-through the miR-1248/CITED2/HIF-1α pathway. Aging 36 32294623
2016 The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through a cAMP-induced substrate switch. Nature communications 36 27874008
2009 CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer. British journal of cancer 35 19904269
2006 Post-transcriptional control of Cited2 by transforming growth factor beta. Regulation via Smads and Cited2 coding region. The Journal of biological chemistry 35 16675452
2020 Long Non-coding RNA FGD5-AS1 Regulates Cancer Cell Proliferation and Chemoresistance in Gastric Cancer Through miR-153-3p/CITED2 Axis. Frontiers in genetics 34 32849774
2010 Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left-right patterning defects. Human molecular genetics 34 20566713
2012 CITED2 is a novel direct effector of peroxisome proliferator-activated receptor γ in suppressing hepatocellular carcinoma cell growth. Cancer 33 23212831
2011 CITED2 controls the hypoxic signaling by snatching p300 from the two distinct activation domains of HIF-1α. Biochimica et biophysica acta 33 21925214
2008 Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency. Cardiovascular research 33 18440989
2018 The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells. The Journal of biological chemistry 32 29794136
2007 CITED2 mediates the paradoxical responses of HIF-1alpha to proteasome inhibition. Oncogene 32 17906695
2007 Regulation of Cited2 expression provides a functional link between translational and transcriptional responses during hypoxia. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 31 17499866
2018 GINS2 promotes cell proliferation and inhibits cell apoptosis in thyroid cancer by regulating CITED2 and LOXL2. Cancer gene therapy 30 30177819
2016 Cited2 Regulates Neocortical Layer II/III Generation and Somatosensory Callosal Projection Neuron Development and Connectivity. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 27307230
2014 CITED2-mediated human hematopoietic stem cell maintenance is critical for acute myeloid leukemia. Leukemia 28 25184385
2021 CircSNHG5 Sponges Mir-495-3p and Modulates CITED2 to Protect Cartilage Endplate From Degradation. Frontiers in cell and developmental biology 27 34277611
2021 CITED2 inhibits STAT1-IRF1 signaling and atherogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 34365659
2010 Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2. International journal of cancer 27 19642106
2023 CITED2 is a conserved regulator of the uterine-placental interface. Proceedings of the National Academy of Sciences of the United States of America 26 36626551
2015 FBXL5 modulates HIF-1α transcriptional activity by degradation of CITED2. Archives of biochemistry and biophysics 26 25956243
2020 CITED2 limits pathogenic inflammatory gene programs in myeloid cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 32697413
2012 Cited2 gene controls pluripotency and cardiomyocyte differentiation of murine embryonic stem cells through Oct4 gene. The Journal of biological chemistry 25 22761414
2020 CITED2 and the modulation of the hypoxic response in cancer. World journal of clinical oncology 24 32728529
2012 A cell-autonomous role of Cited2 in controlling myocardial and coronary vascular development. European heart journal 24 22504313
2008 CITED2 signals through peroxisome proliferator-activated receptor-gamma to regulate death of cortical neurons after DNA damage. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 18495890
2007 CITED2 is expressed in human adrenocortical cells and regulated by basic fibroblast growth factor. The Journal of endocrinology 24 17283246
2019 CITED2 mediates the cross-talk between mechanical loading and IL-4 to promote chondroprotection. Annals of the New York Academy of Sciences 23 30891766
2017 Downregulation of CITED2 contributes to TGFβ-mediated senescence of tendon-derived stem cells. Cell and tissue research 23 28084522
2016 CITED2 Modulates Breast Cancer Metastatic Ability through Effects on IKKα. Molecular cancer research : MCR 23 27216153
2013 CITED2 modulates estrogen receptor transcriptional activity in breast cancer cells. Biochemical and biophysical research communications 23 23811274
2016 CITED2 Cooperates with ISL1 and Promotes Cardiac Differentiation of Mouse Embryonic Stem Cells. Stem cell reports 22 27818139
2015 Acute loss of Cited2 impairs Nanog expression and decreases self-renewal of mouse embryonic stem cells. Stem cells (Dayton, Ohio) 22 25377420
2012 CITED2 mutation links congenital heart defects to dysregulation of the cardiac gene VEGF and PITX2C expression. Biochemical and biophysical research communications 22 22735262
2016 Insulin Downregulates the Transcriptional Coregulator CITED2, an Inhibitor of Proangiogenic Function in Endothelial Cells. Diabetes 21 27561725
2012 Functional significance of SRJ domain mutations in CITED2. PloS one 21 23082118
2008 Overexpression of the transcriptional coregulator Cited2 protects against glucocorticoid-induced atrophy of C2C12 myotubes. Biochemical and biophysical research communications 21 19032942
2006 Generation of conditional Cited2 null alleles. Genesis (New York, N.Y. : 2000) 21 17133411
2020 Investigations of the underlying mechanisms of HIF-1α and CITED2 binding to TAZ1. Proceedings of the National Academy of Sciences of the United States of America 20 32123067
2017 CITED2 affects leukemic cell survival by interfering with p53 activation. Cell death & disease 20 29072699
2016 Cited2 participates in cardiomyocyte apoptosis and maternal diabetes-induced congenital heart abnormality. Biochemical and biophysical research communications 20 27680315
2013 Cited2, a transcriptional modulator protein, regulates metabolism in murine embryonic stem cells. The Journal of biological chemistry 20 24265312
2000 Expression analysis of the chicken homologue of CITED2 during early stages of embryonic development. Mechanisms of development 20 11044621
2021 Potent Inhibition of HIF1α and p300 Interaction by a Constrained Peptide Derived from CITED2. Journal of medicinal chemistry 19 34472840
2015 CITED2 silencing sensitizes cancer cells to cisplatin by inhibiting p53 trans-activation and chromatin relaxation on the ERCC1 DNA repair gene. Nucleic acids research 19 26384430
2009 Conditional deletion of Cited2 results in defective corneal epithelial morphogenesis and maintenance. Developmental biology 19 19632219
2021 Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects. Journal of cellular and molecular medicine 18 33439552
2013 Cited2 is required for the maintenance of glycolytic metabolism in adult hematopoietic stem cells. Stem cells and development 18 24083546
2021 CITED2 coordinates key hematopoietic regulatory pathways to maintain the HSC pool in both steady-state hematopoiesis and transplantation. Stem cell reports 17 34715054
2020 Role of CITED2 in stem cells and cancer. Oncology letters 16 32831926
2017 CITED2 attenuates macrophage recruitment concordant with the downregulation of CCL20 in breast cancer cells. Oncology letters 16 29399152
2021 A gain-of-function mutation in CITED2 is associated with congenital heart disease. Mutation research 15 33706167
2020 Competitive binding of HIF-1α and CITED2 to the TAZ1 domain of CBP from molecular simulations. Physical chemistry chemical physics : PCCP 15 32242581
2019 Novel Point Mutations of CITED2 Gene Are Associated with Non-familial Congenital Heart Disease (CHD) in Sporadic Pediatric Patients. Applied biochemistry and biotechnology 15 31515672
2013 Cited2 in hematopoietic stem cell function. Current opinion in hematology 15 23507959
2010 CITED2 mechanoregulation of matrix metalloproteinases. Annals of the New York Academy of Sciences 15 20392269
2009 Identification of CITED2 as a negative regulator of fracture healing. Biochemical and biophysical research communications 15 19607804
2016 Cited2 protein level in cumulus cells is a biomarker for human embryo quality and pregnancy outcome in one in vitro fertilization cycle. Fertility and sterility 14 26812245

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