Affinage

CIB1

Calcium and integrin-binding protein 1 · UniProt Q99828

Length
191 aa
Mass
21.7 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CIB1 is a ubiquitous EF-hand Ca2+-binding protein with a compact alpha-helical fold and a hydrophobic ligand-binding cleft that functions as a Ca2+-regulated adaptor and regulatory subunit for a broad set of partners controlling cell adhesion, migration, kinase signaling, and Ca2+ homeostasis (PMID:15574431, PMID:21388953). At the platelet membrane it binds the αIIb integrin cytoplasmic tail and competes with talin to restrain agonist-induced αIIbβ3 activation, and in vivo CIB1 loss specifically impairs outside-in signaling, β3 tyrosine phosphorylation, and stable thrombus formation (PMID:16418530, PMID:19691476); its integrin recognition extends to other α-integrin tails through the same hydrophobic pocket (PMID:24011356). CIB1 activates PAK1 in a Ca2+-dependent manner to drive LIM kinase/cofilin-mediated control of cell migration, a PAK1–ERK1/2–MMP2 axis that is required for endothelial migration, proliferation, and angiogenesis in vitro and in CIB1-deficient mice (PMID:16061695, PMID:17975111). It is a Ca2+-gated regulator of stress and cell-cycle kinases, inhibiting ASK1 activation at low Ca2+ by blocking TRAF recruitment and Thr838 autophosphorylation until Ca2+ influx releases the brake to permit p38 activation (PMID:19805025, PMID:31530712), and acting as a regulatory subunit that inhibits PLK3 (PMID:20473878). CIB1 also tunes intracellular Ca2+ signaling by binding all InsP3R isoforms and attenuating InsP3-dependent Ca2+ release in cells (PMID:16723353, PMID:18627437), and it anchors calcineurin B at the sarcolemma to promote NFAT-dependent pathological cardiac hypertrophy (PMID:20639889). Additional roles include facilitating Ca2+-myristoyl-switch–dependent plasma-membrane localization of sphingosine kinase 1 to drive neoplastic transformation (PMID:27941888) and supporting survival signaling through PI3K/AKT and Ras/MEK/ERK, with CIB1 depletion triggering caspase-independent death via nuclear GAPDH accumulation (PMID:22964641). CIB1 abundance is controlled by ubiquitin turnover: the E3 ligase CHIP polyubiquitinates it at K10/K65 for degradation (PMID:33082516), while the deubiquitinase USP14 stabilizes it at K24 to sustain CIB1–PAK1–ERK1/2 signaling (PMID:38993552), and it is mutually stabilized within a TMC6/EVER1–TMC8/EVER2–CIB1 trimeric complex (PMID:32917726). Loss-of-function CIB1 mutations cause epidermodysplasia verruciformis with selective susceptibility to β-HPVs (PMID:30068544).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 Medium

    Established the first physical partner of this novel calcineurin B-like Ca2+-binding protein, linking it to DNA-PKcs and hinting at a nuclear/genome-maintenance role.

    Evidence Yeast two-hybrid plus biochemical binding assay identifying CIB1 (KIP) as a DNA-PKcs partner

    PMID:9372844

    Open questions at the time
    • No functional consequence of the interaction shown
    • Binding interface not mapped
    • Single-lab Y2H-based discovery
  2. 2004 High

    Defined CIB1 as a monomeric four-EF-hand protein with a hydrophobic ligand pocket, providing the structural basis for its promiscuous partner binding and distinguishing it from NCS proteins.

    Evidence X-ray crystallography of Ca2+-bound CIB1 at 2.0 Å with mutational analysis; later NMR of Ca2+/Mg2+ forms mapping the αIIb interface

    PMID:15574431 PMID:21388953

    Open questions at the time
    • Structures of CIB1 bound to most named partners not solved
    • Conformational basis for Ca2+ vs Mg2+ switching only partially defined
  3. 2004 Medium

    Showed CIB1 can act in the nucleus to enhance telomerase activity and telomere length, the first functional output assigned to the protein.

    Evidence Y2H, co-IP, in vitro binding, immunolocalization, and telomerase activity assay with hTERT

    PMID:15190070

    Open questions at the time
    • Mechanism by which CIB1 increases telomerase activity unresolved
    • Ca2+-dependence of the hTERT interaction not addressed
  4. 2005 High

    Identified CIB1 as a Ca2+-dependent PAK1 activator coupling it to LIM kinase/cofilin and cell migration, establishing a cytoskeletal signaling role.

    Evidence In vitro kinase assays, reciprocal co-IP, RNAi loss-of-function and overexpression with migration phenotypes

    PMID:16061695

    Open questions at the time
    • Structural basis of PAK1 inhibitory-switch engagement not solved
    • How Ca2+ gates activation mechanistically unclear
  5. 2006 High

    Placed CIB1 as a negative regulator of integrin αIIbβ3 activation via competition with talin, and a genetic requirement for spermatogenesis and cell-cycle control.

    Evidence Megakaryocyte overexpression/RNAi with integrin activation assays; Cib1-/- knockout mice with testis histology and MEF proliferation

    PMID:16418530 PMID:16982698

    Open questions at the time
    • Direct structural proof of talin competition at the αIIb tail not provided
    • Molecular link between CIB1 and Cdc2/Cdk1 in germ cells undefined
  6. 2006 High

    Revealed CIB1 as a Ca2+-sensitive InsP3R-binding protein with paradoxical activity—activating channel gating in vitro yet attenuating cellular Ca2+ signaling—implicating it in Ca2+ homeostasis.

    Evidence Pull-downs, single-channel patch clamp, and Ca2+ imaging with overexpression; later in vivo shRNA/overexpression FURA-2 imaging

    PMID:16723353 PMID:18627437

    Open questions at the time
    • Reconciliation of in vitro activation vs cellular attenuation not fully resolved
    • InsP3R-binding site not mapped
  7. 2009 High

    Defined CIB1 as a Ca2+-gated brake on ASK1 stress signaling, blocking TRAF2 recruitment and Thr838 autophosphorylation, with Ca2+ influx relieving inhibition.

    Evidence Co-IP, in vitro kinase assays, mechanistic Thr838 mutant, Ca2+ manipulation, and cell death assays; later confirmed in Cib1-/- platelets with p38 readout

    PMID:19805025 PMID:31530712

    Open questions at the time
    • Discrepancy in adaptor identity (TRAF2 vs TRAF6) across systems
    • Stoichiometry of the Ca2+-driven dissociation not quantified
  8. 2009 High

    Showed CIB1 is required in vivo for thrombosis, assigning its platelet function specifically to outside-in αIIbβ3 signaling.

    Evidence Cib1-/- mice with bleeding, FeCl3 carotid thrombosis, platelet spreading assays, and β3 phosphorylation immunoblotting

    PMID:19691476

    Open questions at the time
    • Direct connection between CIB1 and β3 tyrosine phosphorylation machinery not established
  9. 2010 High

    Established CIB1 as a sarcolemmal anchor for calcineurin B that drives NFAT-dependent pathological cardiac hypertrophy.

    Evidence Y2H, immunolocalization, Cib1-/- and inducible cardiac-overexpression mice, pressure-overload models, NFAT reporter, epistasis with calcineurin Aβ-null mice

    PMID:20639889

    Open questions at the time
    • How CIB1 selectively couples calcineurin to L-type Ca2+ channels mechanistically unclear
  10. 2011 Medium

    Identified CIB1 as a constitutive, Ca2+-dependent inhibitory regulatory subunit of PLK3.

    Evidence Co-IP in vitro and in vivo with in vitro kinase assays and Ca2+ manipulation

    PMID:20473878

    Open questions at the time
    • Cellular and physiological consequence of PLK3 inhibition not established
    • Single-lab finding
  11. 2014 Medium

    Connected CIB1 to telomere protection, showing it bridges TRF2 and DNA-PKcs and that its loss provokes telomere damage and senescence.

    Evidence Co-IP, ChIP, immunolocalization, telomere dysfunction assays, and flow cytometry

    PMID:25012820

    Open questions at the time
    • Whether telomeric and DNA-PKcs roles are direct or scaffold-mediated unresolved
    • Single-lab study
  12. 2016 Medium

    Showed CIB1 promotes oncogenic transformation by recruiting sphingosine kinase 1 to the plasma membrane through a Ca2+-myristoyl switch.

    Evidence Subcellular fractionation, enzymatic activity assays, transformation assays, shRNA/overexpression, and SK1 epistasis

    PMID:27941888

    Open questions at the time
    • Structural detail of the Ca2+-myristoyl switch with SK1 not defined
    • Single-lab finding
  13. 2017 High

    Identified CIB1 as a modulator of type III CD38, with cellular cADPR levels tracking CIB1 abundance.

    Evidence Y2H, co-IP, ELISA, BiFC, shRNA and CRISPR knockout with cADPR quantification

    PMID:28720704

    Open questions at the time
    • Mechanism by which CIB1 binding alters CD38 catalysis not defined
  14. 2018 Medium

    Linked CIB1 to antiviral keratinocyte biology and human disease, identifying it as part of an EVER1/EVER2 complex and a restriction factor whose loss causes epidermodysplasia verruciformis.

    Evidence Co-IP, immunofluorescence, Western blotting in patient and control keratinocytes, HPV E5/E8 interaction, and patient genetics

    PMID:30068544

    Open questions at the time
    • Mechanism of β-HPV restriction by the EVER1/EVER2/CIB1 complex not defined
    • Single-lab finding
  15. 2020 High

    Defined the ubiquitin-controlled turnover of CIB1, identifying CHIP-mediated degradation at K10/K65 and mutual stabilization within the TMC6/TMC8/CIB1 trimer.

    Evidence Mass spectrometry, co-IP, ubiquitination assays with site-directed mutagenesis, metastasis assays, and TMC6/TMC8 knockout mice

    PMID:32917726 PMID:33082516

    Open questions at the time
    • Signals regulating CHIP-CIB1 engagement unknown
    • Whether trimer stabilization competes with CHIP not tested
  16. 2024 Medium

    Showed USP14 stabilizes CIB1 by removing K48-linked ubiquitin at K24 to sustain CIB1-PAK1-ERK1/2 signaling and drug resistance.

    Evidence Co-IP, ubiquitination assays with site identification, xenografts, and AAV transduction with lenvatinib resistance readouts

    PMID:38993552

    Open questions at the time
    • How USP14 and CHIP balance is regulated unknown
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single small EF-hand adaptor selects among its many partners in a given cell, and what determines which Ca2+-gated output dominates physiologically.
  • No quantitative affinity/competition ranking across partners
  • Tissue-specific partner usage undefined
  • Most CIB1-partner co-structures unsolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0140299 molecular sensor activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-109582 Hemostasis 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ASK1CD38ITGA2BITPR1PAK1PLK3PPP3R1SPHK1
Complex memberships
TMC6/EVER1-TMC8/EVER2-CIB1 trimerTRF2-DNA-PKcs telomere complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Crystal structure of Ca2+-bound CIB1 determined at 2.0 Å resolution, revealing a compact alpha-helical protein with four EF-hands (last two binding calcium) and a hydrophobic pocket implicated in ligand binding. CIB1 is largely monomeric whether ligand-bound or free, distinguishing it from NCS proteins, and shares structural similarity with calcineurin B and neuronal calcium sensor family proteins. X-ray crystallography, mutational analysis The Journal of biological chemistry High 15574431
2011 Solution structures of Ca2+-CIB1 and Mg2+-CIB1 determined by NMR; EF-hand III is directly involved in binding to the integrin αIIb cytoplasmic domain, and C-terminal helix of Ca2+-CIB1 is displaced upon αIIb binding. Solution NMR spectroscopy, chemical shift perturbation, nitroxide surface probe The Journal of biological chemistry High 21388953
1997 CIB1 (referred to as KIP, a novel calcium-binding protein with ~26% identity to calcineurin B) was identified as a binding partner of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) via yeast two-hybrid analysis, satisfying both high genetic and biochemical stringency. Yeast two-hybrid, biochemical binding assay Mutation research Medium 9372844
2004 CIB1 (KIP) binds directly to the catalytic subunit of telomerase (hTERT) independently of telomerase RNA or telomeric DNA; CIB1 co-localizes with hTERT in the nucleus; overexpression of CIB1 increases endogenous telomerase activity and results in telomere elongation after 60 population doublings. Yeast two-hybrid, co-immunoprecipitation, immunolocalization, in vitro binding, telomerase activity assay The Journal of biological chemistry Medium 15190070
2005 CIB1 directly and specifically interacts with PAK1 in a calcium-dependent manner, binding within discrete regions surrounding the PAK1 inhibitory switch domain; this interaction activates PAK1 both in vitro and in vivo. CIB1 overexpression decreases cell migration on fibronectin via a PAK1- and LIM kinase-dependent increase in cofilin phosphorylation. RNAi-mediated depletion of CIB1 increases cell migration and reduces adhesion-induced PAK1 activation and cofilin phosphorylation. In vitro kinase assay, co-immunoprecipitation, RNAi knockdown, cell migration assay, western blotting The Journal of cell biology High 16061695
2006 CIB1 is an endogenous inhibitor of agonist-induced αIIbβ3 integrin activation in platelets; overexpression in megakaryocytes blocks agonist-induced αIIbβ3 activation, while RNAi reduction of CIB1 enhances activation. CIB1 appears to inhibit integrin activation by competing with talin for binding to the αIIb tail. Overexpression in megakaryocytes, RNAi knockdown, integrin activation assay, competitive binding The Journal of cell biology High 16418530
2006 CIB1 is essential for spermatogenesis in mice; Cib1-/- males are sterile due to disruption of haploid phase of spermatogenesis with increased germ cell apoptosis and loss of elongated spermatids. Cib1-/- testes show increased Cdc2/Cdk1 mRNA and protein. Cib1-/- MEFs show slower growth rate, suggesting CIB1 regulates cell cycle. Homologous recombination knockout, histology, Western blotting, RT-PCR, MEF proliferation assay Molecular and cellular biology High 16982698
2006 CIB1 binds to all mammalian InsP3R isoforms in a calcium-sensitive manner dependent on its two functional EF-hands; CIB1 activates InsP3R channel gating in the absence of InsP3 in vitro, but overexpression of CIB1 attenuates InsP3R-dependent Ca2+ signaling in cells; pre-exposure to CIB1 in vitro reduces channels available for subsequent InsP3 stimulation. Pull-down, patch-clamp electrophysiology, Ca2+ imaging, overexpression The Journal of biological chemistry High 16723353
2007 CIB1 and CaBP1 bind to the IQ motifs in the myo1c regulatory domain, competing with calmodulin for binding; both proteins co-localize with myo1c in vivo and binding is enhanced in the presence of calcium. Pull-down experiments, fluorescence microscopy co-localization, competitive binding assays Journal of muscle research and cell motility Medium 17994197
2007 CIB1 regulates endothelial cell migration, proliferation, and tubule formation; loss of CIB1 (shRNA or knockout) decreases PAK1 activation, ERK1/2 activation, and MMP-2 expression. CIB1-/- mice show reduced growth factor-induced microvessel sprouting, impaired ischemia-induced retinal angiogenesis, and reduced hindlimb adaptive angiogenesis with decreased PAK1 activation. shRNA knockdown, CIB1-/- mice, ex vivo organ culture, in vivo Matrigel plugs, Western blotting Circulation research High 17975111
2008 CIB1 acts as a general inhibitor of InsP3-dependent Ca2+ release in vivo; stable and transient shRNA depletion of CIB1 increases Ca2+ responses to InsP3-generating ligands (ATP, UTP, carbachol), while overexpression has the opposite effect; this is dependent on ER thapsigargin-sensitive Ca2+ stores and likely mediated via InsP3 receptor interaction. shRNA depletion, overexpression, FURA-2 Ca2+ imaging Journal of neurochemistry Medium 18627437
2009 CIB1 binds to ASK1 and negatively regulates ASK1-mediated stress signaling: CIB1 interferes with TRAF2 recruitment to ASK1 and inhibits ASK1 autophosphorylation on Thr-838, thereby blocking ASK1 activation. Ca2+ influx reverses the inhibitory effect of CIB1 on ASK1 activation. CIB1 mitigates apoptotic cell death induced by TNF-α in MCF7 cells or 6-OHDA in dopaminergic cells. Co-immunoprecipitation, in vitro kinase assay, Ca2+ manipulation, cell death assay Proceedings of the National Academy of Sciences of the United States of America High 19805025
2009 CIB1 deficiency (genetic knockout) impairs in vivo thrombosis: Cib1-/- mice show increased tail bleeding time, rebleeding, delayed carotid artery occlusion, and unstable thrombus formation. Outside-in signaling-dependent β3 tyrosine phosphorylation is significantly reduced in Cib1-/- platelets; platelet spreading on fibrinogen is impaired but filopodia formation is unaffected. Inside-out signaling (agonist-induced aggregation and fibrinogen binding) is unaffected. Cib1-/- knockout mice, tail bleeding assay, FeCl3-induced carotid thrombosis, platelet spreading assay, Western blotting Journal of thrombosis and haemostasis High 19691476
2010 CIB1 is a regulator of pathological cardiac hypertrophy acting by anchoring calcineurin to the sarcolemma via direct interaction with calcineurin B (identified by yeast two-hybrid). CIB1 localizes primarily to the sarcolemma in mouse and human myocardium, coordinating calcineurin activation with L-type Ca2+ channel. Cib1-/- mice show reduced hypertrophy, fibrosis, and NFAT activity after pressure overload but normal physiological hypertrophy; cardiac-specific CIB1 overexpression enhances hypertrophic response in a Ppp3cb (calcineurin Aβ)-dependent manner. Yeast two-hybrid, immunolocalization, Cib1-/- knockout mice, inducible transgenic overexpression, pressure overload and exercise models, NFAT reporter assay Nature medicine High 20639889
2011 CIB1 constitutively interacts with PLK3 (polo-like kinase 3) in vitro and in vivo independently of intracellular Ca2+; CIB1 binding inhibits PLK3 kinase activity in vitro and in vivo in a Ca2+-dependent manner, suggesting CIB1 is a regulatory subunit of PLK3. Co-immunoprecipitation, in vitro kinase assay, Ca2+ manipulation International journal of cancer Medium 20473878
2012 CIB1 depletion in neuroblastoma and breast cancer cells promotes non-apoptotic, caspase-independent cell death requiring nuclear GAPDH accumulation. CIB1 depletion disrupts PI3K/AKT and Ras/MEK/ERK signaling synergistically; AKT inhibition alone maximally induced GAPDH nuclear accumulation while MEK/ERK inhibition had no effect alone; concurrent GAPDH nuclear accumulation and ERK inhibition were required to induce DNA damage response and subsequent cell death. RNAi depletion, pharmacological inhibitors, immunoblotting, immunofluorescence, cell death assay Oncogene Medium 22964641
2013 CIB1 interacts with multiple α-integrin cytoplasmic tails beyond αIIb via a conserved hydrophobic binding pocket; novel in vivo interactions with other integrin complexes confirmed by co-immunoprecipitation; isothermal titration calorimetry shows binding is driven by hydrophobic interactions. Co-immunoprecipitation, solid-phase competitive binding assay, isothermal titration calorimetry, all-atom replica exchange discrete molecular dynamics Biochemistry Medium 24011356
2014 CIB1 (KIP) interacts with TRF2 and DNA-PKcs at telomeres; CIB1 is required for the association between TRF2 and DNA-PKcs; CIB1 binding to TRF2 enhances TRF2 telomere-binding activity; depletion of CIB1 induces DNA damage foci at telomeres, growth arrest, cellular senescence, and altered cell cycle distribution. Co-immunoprecipitation, chromatin immunoprecipitation, immunolocalization, telomere dysfunction assay, flow cytometry The Biochemical journal Medium 25012820
2016 CIB1 facilitates agonist-induced plasma membrane localization of sphingosine kinase 1 (SK1) via a Ca2+-myristoyl switch mechanism; CIB1 overexpression alone drives SK1 to the plasma membrane, enhances membrane-associated SK1 enzymatic activity, and is sufficient to drive neoplastic transformation in an SK1-dependent manner. CIB1 inhibition also blocks neoplastic growth induced by oncogenic Ras. Subcellular fractionation, enzymatic activity assay, transformation assay, shRNA knockdown, overexpression Oncogene Medium 27941888
2017 CIB1 binds specifically to the catalytic domain of type III CD38 (cytosol-facing orientation) as shown by yeast two-hybrid, immunoprecipitation, ELISA, and bimolecular fluorescence complementation; the N-terminus of CIB1 is the interacting domain. shRNA knockdown and CRISPR knockout of CIB1 demonstrate a direct correlation between cellular cADPR levels and CIB1 levels, establishing CIB1 as a modulator of type III CD38 activity. Yeast two-hybrid, co-immunoprecipitation, ELISA, bimolecular fluorescence complementation, shRNA knockdown, CRISPR knockout, cADPR quantification Proceedings of the National Academy of Sciences of the United States of America High 28720704
2018 CIB1 forms a complex with EVER1 (TMC6) and EVER2 (TMC8) in keratinocytes; CIB1 is not expressed in EVER1- or EVER2-deficient cells. CIB1 interacts with HPV E5 (α-HPV16) and E8 (γ-HPV4) proteins, suggesting a role as a restriction factor against HPVs. Loss-of-function CIB1 mutations in humans cause epidermodysplasia verruciformis with selective susceptibility to β-HPVs. Co-immunoprecipitation, immunofluorescence, Western blotting in patient-derived and control keratinocytes, patient genetic analysis The Journal of experimental medicine Medium 30068544
2019 In resting platelets, CIB1 associates with ASK1 at low Ca2+ concentrations and inhibits ASK1 activation; agonist-induced increase in intracellular Ca2+ causes dissociation of CIB1 from ASK1, allowing ASK1 dimerization via N-terminal coiled-coil domains, TRAF6 recruitment, and autophosphorylation of ASK1 Thr838, resulting in full p38 MAPK activation. Genetic ablation of Cib1 augments agonist-induced Ask1/p38 activation. Co-immunoprecipitation, kinase assay, Ca2+ chelation/ionophore experiments, Cib1-/- mice, Western blotting The Biochemical journal High 31530712
2020 CHIP (an E3 ubiquitin ligase) interacts with CIB1 and promotes its polyubiquitination and proteasomal degradation; lysine residues K10 and K65 of CIB1 are the ubiquitinated sites. CHIP-mediated CIB1 downregulation suppresses EMT, migration, and metastasis of lung adenocarcinoma cells. Mass spectrometry, co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, in vitro and in vivo metastasis assays Cell death and differentiation High 33082516
2020 TMC6 and TMC8 form a protein complex in mouse and human T cells and additionally interact with CIB1 to form TMC6-TMC8-CIB1 trimers; TMC6 and TMC8 protect CIB1 from ubiquitination and proteasomal degradation; reciprocally, CIB1 is needed for stabilizing TMC6 and TMC8 levels. Co-immunoprecipitation, mass spectrometry, Western blotting, TMC6 and TMC8 knockout mice The Journal of biological chemistry Medium 32917726
2024 USP14 (a deubiquitinase) directly interacts with and stabilizes CIB1 by reversing K48-linked proteolytic ubiquitination at K24, facilitating the CIB1-PAK1-ERK1/2 signaling axis; USP14 silencing attenuates lenvatinib resistance; adeno-associated virus-mediated CIB1 transduction promotes lenvatinib resistance while CIB1 knockdown resensitizes tumors to lenvatinib. Co-immunoprecipitation, ubiquitination assay with site identification, in vitro and in vivo xenograft models, AAV transduction International journal of biological sciences Medium 38993552

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes & development 915 7649471
2006 DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest. Current biology : CB 198 16631585
1998 Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development. BioEssays : news and reviews in molecular, cellular and developmental biology 171 10048302
1999 Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex. The EMBO journal 144 9927424
2011 Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors. Trends in cell biology 134 22154077
2009 p57KIP2: "Kip"ing the cell under control. Molecular cancer research : MCR 128 19934273
2002 Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Oncogene 114 12386815
2001 lin-35 Rb and cki-1 Cip/Kip cooperate in developmental regulation of G1 progression in C. elegans. Development (Cambridge, England) 110 11684669
2018 The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. The Journal of experimental medicine 109 30068544
2000 Mechanism for inactivation of the KIP family cyclin-dependent kinase inhibitor genes in gastric cancer cells. Cancer research 105 10667572
1999 RhoA stimulates p27(Kip) degradation through its regulation of cyclin E/CDK2 activity. The Journal of biological chemistry 105 9920882
1997 Induction of Cip/Kip and Ink4 cyclin dependent kinase inhibitors by interferon-alpha in hematopoietic cell lines. Oncogene 105 9053838
2004 Structural and biochemical characterization of CIB1 delineates a new family of EF-hand-containing proteins. The Journal of biological chemistry 100 15574431
2013 Blue light-dependent interaction between cryptochrome2 and CIB1 regulates transcription and leaf senescence in soybean. The Plant cell 95 24272488
1998 Reduction in levels of the cyclin-dependent kinase inhibitor p27(kip-1) coupled with transforming growth factor beta neutralization induces cell-cycle entry and increases retroviral transduction of primitive human hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America 94 9789031
1999 Expression of p27(kip) and other cell cycle regulators in malignant peripheral nerve sheath tumors and neurofibromas: the emerging role of p27(kip) in malignant transformation of neurofibromas. The American journal of pathology 87 10595919
2010 CIB1 is a regulator of pathological cardiac hypertrophy. Nature medicine 83 20639889
2005 Overexpression of p27 Kip 1, probability of cell cycle exit, and laminar destination of neocortical neurons. Cerebral cortex (New York, N.Y. : 1991) 83 15647527
2004 Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast transformation. Journal of virology 74 15564458
2005 Essential role of CIB1 in regulating PAK1 activation and cell migration. The Journal of cell biology 71 16061695
2000 Growth inhibition in G(1) and altered expression of cyclin D1 and p27(kip-1 )after forced connexin expression in lung and liver carcinoma cells. Journal of cellular biochemistry 71 10972973
1999 Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 71 10506612
2006 CIB1 is an endogenous inhibitor of agonist-induced integrin alphaIIbbeta3 activation. The Journal of cell biology 70 16418530
2009 Cip/Kip cyclin-dependent protein kinase inhibitors and the road to polyploidy. Cell division 68 19490616
2006 Downregulation of the KIP family members p27(KIP1) and p57(KIP2) by SKP2 and the role of methylation in p57(KIP2) inactivation in nonsmall cell lung cancer. International journal of cancer 68 16988944
2006 CIB1 is essential for mouse spermatogenesis. Molecular and cellular biology 64 16982698
2003 The p27cip/kip ortholog dacapo maintains the Drosophila oocyte in prophase of meiosis I. Development (Cambridge, England) 64 12588841
2006 A cell-autonomous requirement for Cip/Kip cyclin-kinase inhibitors in regulating neuronal cell cycle exit but not differentiation in the developing spinal cord. Developmental biology 61 17123502
1997 Interaction between DNA-dependent protein kinase and a novel protein, KIP. Mutation research 60 9372844
2018 CIB1 and CO interact to mediate CRY2-dependent regulation of flowering. EMBO reports 58 30126927
2016 CIB1: a small protein with big ambitions. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 57 27118676
2017 Cytosolic interaction of type III human CD38 with CIB1 modulates cellular cyclic ADP-ribose levels. Proceedings of the National Academy of Sciences of the United States of America 54 28720704
2003 Induction of G1 phase arrest in MCF human breast cancer cells by pentagalloylglucose through the down-regulation of CDK4 and CDK2 activities and up-regulation of the CDK inhibitors p27(Kip) and p21(Cip). Biochemical pharmacology 53 12781329
2006 CIB1, a ubiquitously expressed Ca2+-binding protein ligand of the InsP3 receptor Ca2+ release channel. The Journal of biological chemistry 51 16723353
2001 Hepatitis B virus X protein increases expression of p21(Cip-1/WAF1/MDA6) and p27(Kip-1) in primary mouse hepatocytes, leading to reduced cell cycle progression. Hepatology (Baltimore, Md.) 50 11679961
2009 CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1. Proceedings of the National Academy of Sciences of the United States of America 49 19805025
2002 Underexpression of p27/Kip in thyroid papillary microcarcinomas with gross metastatic disease. Archives of otolaryngology--head & neck surgery 48 11886339
2013 Multiple functions of Kip-related protein5 connect endoreduplication and cell elongation. Plant physiology 41 23426196
2004 DNA-protein kinase catalytic subunit-interacting protein KIP binds telomerase by interacting with human telomerase reverse transcriptase. The Journal of biological chemistry 41 15190070
1990 Early determination in the C. elegans embryo: a gene, cib-1, required to specify a set of stem-cell-like blastomeres. Development (Cambridge, England) 41 2351058
2005 Absence of p21(CIP 1), p27(KIP 1) and p 57(KIP 2) methylation in MDS and AML. Leukemia research 39 15936816
2012 CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling. Oncogene 38 22964641
2002 Molecular staging of colorectal cancer in African-American and Caucasian patients using phenotypic expression of p53, Bcl-2, MUC-1 AND p27(kip-1). International journal of cancer 38 11802199
2002 Inverse relationship between p27/Kip.1 and the F-box protein Skp2 in human astrocytic gliomas by immunohistochemistry and Western blot. Neuroscience letters 38 12133571
2013 Ectopic expression of Kip-related proteins restrains root-knot nematode-feeding site expansion. The New phytologist 36 23574394
2009 CIB1 deficiency results in impaired thrombosis: the potential role of CIB1 in outside-in signaling through integrin alpha IIb beta 3. Journal of thrombosis and haemostasis : JTH 35 19691476
2006 Connective tissue growth factor/CCN2 stimulates actin disassembly through Akt/protein kinase B-mediated phosphorylation and cytoplasmic translocation of p27(Kip-1). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35 16790529
2005 The maize aberrant pollen transmission 1 gene is a SABRE/KIP homolog required for pollen tube growth. Genetics 35 16299389
2007 CIB1 regulates endothelial cells and ischemia-induced pathological and adaptive angiogenesis. Circulation research 33 17975111
2014 CIB1 synergizes with EphrinA2 to regulate Kaposi's sarcoma-associated herpesvirus macropinocytic entry in human microvascular dermal endothelial cells. PLoS pathogens 32 24550731
2015 Fenofibrate induces G0/G1 phase arrest by modulating the PPARα/FoxO1/p27 kip pathway in human glioblastoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 25566967
2014 Genetic characterization of the role of the Cip/Kip family of proteins as cyclin-dependent kinase inhibitors and assembly factors. Molecular and cellular biology 31 24515438
2019 Effect of 5-Aza-2'-Deoxycytidine in Comparison to Valproic Acid and Trichostatin A on Histone Deacetylase 1, DNA Methyltransferase 1, and CIP/KIP Family (p21, p27, and p57) Genes Expression, Cell Growth Inhibition, and Apoptosis Induction in Colon Cancer SW480 Cell Line. Advanced biomedical research 30 31516890
2011 FBF represses the Cip/Kip cell-cycle inhibitor CKI-2 to promote self-renewal of germline stem cells in C. elegans. The EMBO journal 30 21822213
2005 Epigenetic inactivation of the CIP/KIP cell-cycle control pathway in acute leukemias. American journal of hematology 29 16315255
2016 CIB1 contributes to oncogenic signalling by Ras via modulating the subcellular localisation of sphingosine kinase 1. Oncogene 28 27941888
2010 Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle progression in 11q13-amplified head and neck squamous cell carcinoma cells. Molecular and cellular biology 28 20805359
2015 CIB1 depletion impairs cell survival and tumor growth in triple-negative breast cancer. Breast cancer research and treatment 26 26105795
2013 Identification of novel integrin binding partners for calcium and integrin binding protein 1 (CIB1): structural and thermodynamic basis of CIB1 promiscuity. Biochemistry 26 24011356
2011 Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1 in breast cancer cells. International journal of cancer 26 20473878
2008 Characterization of calcium- and integrin-binding protein 1 (CIB1) knockout platelets: potential compensation by CIB family members. Thrombosis and haemostasis 26 18989529
2013 The role of p21Waf1/CIP1 as a Cip/Kip type cell-cycle regulator in oral squamous cell carcinoma (Review). Medicina oral, patologia oral y cirugia bucal 25 23385498
2007 CIB1 and CaBP1 bind to the myo1c regulatory domain. Journal of muscle research and cell motility 25 17994197
2006 Methylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in chronic lymphocytic leukaemia in Chinese patients. Journal of clinical pathology 25 16565223
2014 The activity and stability of the intrinsically disordered Cip/Kip protein family are regulated by non-receptor tyrosine kinases. Journal of molecular biology 24 25463440
2008 Sweet taste receptor interacting protein CIB1 is a general inhibitor of InsP3-dependent Ca2+ release in vivo. Journal of neurochemistry 22 18627437
2024 CIP/KIP and INK4 families as hostages of oncogenic signaling. Cell division 21 38561743
2021 Discovery and Development of Cyclic Peptide Inhibitors of CIB1. ACS medicinal chemistry letters 21 34795874
2007 Expression of Bax, p53, and p27/kip in patients with papillary thyroid carcinoma with or without cervical nodal metastasis. American journal of otolaryngology 21 17162129
2020 CHIP-mediated CIB1 ubiquitination regulated epithelial-mesenchymal transition and tumor metastasis in lung adenocarcinoma. Cell death and differentiation 19 33082516
2015 An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing replicative stress. Cell death and differentiation 19 26292757
2012 Development of mice without Cip/Kip CDK inhibitors. Biochemical and biophysical research communications 19 23000166
2011 Solution structures of Ca2+-CIB1 and Mg2+-CIB1 and their interactions with the platelet integrin alphaIIb cytoplasmic domain. The Journal of biological chemistry 19 21388953
2010 Tumor growth and angiogenesis is impaired in CIB1 knockout mice. Journal of angiogenesis research 19 20804551
2010 Tumor necrosis factor-α regulates p27 kip expression and apoptosis in smooth muscle cells of human carotid plaques via forkhead transcription factor O1. Experimental and molecular pathology 19 21075101
2005 Increase in Ara-C cytotoxicity in the presence of valproate, a histone deacetylase inhibitor, is associated with the concurrent expression of cyclin D1 and p27(Kip 1) in acute myeloblastic leukemia cells. Leukemia research 19 15936818
2017 Two maize Kip-related proteins differentially interact with, inhibit and are phosphorylated by cyclin D-cyclin-dependent kinase complexes. Journal of experimental botany 18 28369656
2017 The Emerging Roles of CIB1 in Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 18 29017172
2019 Calcium-induced dissociation of CIB1 from ASK1 regulates agonist-induced activation of the p38 MAPK pathway in platelets. The Biochemical journal 16 31530712
2008 Molecular characterization of the sheep CIB1 gene. Molecular biology reports 16 18989754
2004 PAkt, cyclin D1 and p27/Kip.1 in glioblastomas with and without EGFR amplification and PTEN mutation. Anticancer research 16 15517868
2001 Cip/Kip cell-cycle inhibitors: a neuro-oncological perspective. Journal of neuro-oncology 16 11407593
2001 Expression of Ol-KIP, a cyclin-dependent kinase inhibitor, in embryonic and adult medaka (Oryzias latipes) central nervous system. Developmental dynamics : an official publication of the American Association of Anatomists 16 11747078
1999 Cell-cycle inhibitor p27/Kip-1 expression in non-astrocytic and non-oligodendrocytic human nervous system tumors. Neuroscience letters 16 10320006
2011 Proteomic identification of CIB1 as a potential diagnostic factor in hepatocellular carcinoma. Journal of biosciences 15 21857112
2001 Expression of second class of KIP protein p57KIP2 in human colorectal carcinoma. International journal of oncology 15 11408920
1997 TGFB, TGFB Receptors, Ki-67, and p27(Kip)l Expression in Papillary Thyroid Carcinomas. Endocrine pathology 15 12114790
2014 Calcium- and integrin-binding protein-1 is down-regulated in the sperm of patients with oligoasthenozoospermia : CIB1 expression in patients with oligoasthenozoospermia. Journal of assisted reproduction and genetics 14 24464679
2011 The role of the LH subdomain in the function of the Cip/Kip cyclin-dependent kinase regulators. Biophysical journal 14 21575583
2000 P16Ink4a tumor suppressor function in lung cancer cells involves cyclin-dependent kinase 2 inhibition by Cip/Kip protein redistribution. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 14 11063124
2021 The CIB1 transcription factor regulates light- and heat-inducible cell elongation via a two-step HLH/bHLH system. Journal of experimental botany 13 33258952
2020 Expression of a TMC6-TMC8-CIB1 heterotrimeric complex in lymphocytes is regulated by each of the components. The Journal of biological chemistry 13 32917726
2017 Light-Regulated Protein Kinases Based on the CRY2-CIB1 System. Methods in molecular biology (Clifton, N.J.) 13 28293892
2016 Unfolded Protein Response (UPR) Regulator Cib1 Controls Expression of Genes Encoding Secreted Virulence Factors in Ustilago maydis. PloS one 13 27093436
2002 Pituitary hyperplasia in glycoprotein hormone alpha subunit-, p18(INK4C)-, and p27(kip-1)-null mice: analysis of proteins influencing p27(kip-1) ubiquitin degradation. The American journal of pathology 13 11891212
2019 CIB1 depletion with docetaxel or TRAIL enhances triple-negative breast cancer cell death. Cancer cell international 12 30740034
2017 CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1. Scientific reports 12 28939911
2017 The KIP/CIP family members p21^{Waf1/Cip1} and p57^{Kip2} as diagnostic markers for breast cancer. Cancer biomarkers : section A of Disease markers 11 28106536
2014 DNA-PKcs-interacting protein KIP binding to TRF2 is required for the maintenance of functional telomeres. The Biochemical journal 11 25012820
2024 Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma. International journal of biological sciences 10 38993552

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