Affinage

CIP2A

Protein CIP2A · UniProt Q8TCG1

Length
905 aa
Mass
102.2 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CIP2A is an oncoprotein whose central activity is the inhibition of the tumor-suppressor phosphatase PP2A, through which it stabilizes c-Myc and drives proliferative signaling in multiple cancers (PMID:17632056). Structurally, CIP2A forms homodimers via a conserved N-terminal region required for efficient binding to the PP2A B56 regulatory subunits, and dimerization or B56 binding is needed for CIP2A's own stability (PMID:28174209). It inhibits PP2A-B56α by displacing the PP2A-A scaffold subunit and hijacking B56α and the catalytic PP2Ac subunit into a CIP2A-B56α-PP2Ac pseudotrimer, while simultaneously occluding the LxxIxE substrate-binding pocket of B56α; targeted mutation of the N-terminal head domain blunts MYC expression and MEK phosphorylation and abrogates triple-negative breast cancer growth in vivo (PMID:36854761). By suppressing PP2A activity toward c-Myc-S62, Akt, and p27Kip1, CIP2A sustains growth and cell-cycle progression (PMID:17632056, PMID:20729919, PMID:27694903). CIP2A additionally associates with mTORC1 as an allosteric inhibitor of mTORC1-associated PP2A, enhancing growth signaling and suppressing autophagy, and is itself subject to p62/SQSTM1-dependent autophagic degradation upon nutrient deprivation, forming a feedback circuit that couples nutrient status to c-Myc stability (PMID:24590173). Beyond phosphatase inhibition, CIP2A performs PP2A-independent mitotic functions: it binds the polo-box domain of Plk1 to block APC/C-Cdh1-mediated proteolysis and maintain Plk1 activity (PMID:23983103), and it forms a mitosis-specific complex with TOPBP1 and MDC1 that is nuclear-excluded during interphase but accesses chromatin upon nuclear envelope breakdown to recruit TOPBP1 to mitotic DNA lesions and prevent lethal chromosome mis-segregation—a function selectively essential in BRCA1/2-deficient cancers, establishing CIP2A as a synthetic-lethal target (PMID:35121901, PMID:35842428, PMID:34145035). CIP2A also directly binds PKM2 to induce its tetramerization and mitochondrial relocalization, promoting oxidative phosphorylation in lung cancer cells (PMID:38321019). CIP2A levels are controlled transcriptionally by factors including HDAC1, HOXB13, and Elk1 (PMID:27029072, PMID:30181389, PMID:26824320, PMID:28027514) and contribute to physiological roles in spermatogonial progenitor maintenance and T-cell activation (PMID:22461891, PMID:27100879).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2007 High

    Established CIP2A's founding identity: it was unknown how c-Myc escaped PP2A-mediated turnover, and this work showed CIP2A binds c-Myc, inhibits PP2A toward c-Myc-S62, and is itself transforming.

    Evidence Co-IP, PP2A activity assays, cell transformation and in vivo tumor assays

    PMID:17632056

    Open questions at the time
    • Did not resolve the structural basis of PP2A inhibition
    • Did not distinguish direct versus indirect c-Myc binding mechanism
  2. 2010 Medium

    Extended PP2A inhibition to Akt signaling, addressing whether CIP2A acts beyond c-Myc by showing it suppresses Akt-directed PP2A activity to elevate phospho-Akt.

    Evidence siRNA and overexpression with Akt-substrate PP2A activity assays and xenograft in hepatocellular carcinoma

    PMID:20729919

    Open questions at the time
    • Single lab
    • Did not define which PP2A holoenzyme mediates the Akt effect
  3. 2013 High

    Revealed a PP2A-independent mitotic role, answering how CIP2A affects mitosis: it binds the Plk1 polo-box domain to block APC/C-Cdh1 degradation and sustain Plk1 activity.

    Evidence Subcellular fractionation, Co-IP, Plk1 kinase and APC/C-Cdh1 ubiquitination assays, siRNA phenotyping

    PMID:23983103

    Open questions at the time
    • Did not map the Plk1-binding region on CIP2A
    • Relationship to the later TOPBP1 mitotic complex unaddressed
  4. 2014 High

    Connected CIP2A to nutrient sensing and autophagy, showing it allosterically inhibits mTORC1-associated PP2A and is degraded via p62-dependent autophagy under starvation, forming a feedback loop to c-Myc.

    Evidence RNAi screen, reciprocal Co-IP, PP2A activity, autophagy flux and ubiquitination assays

    PMID:24590173

    Open questions at the time
    • E3 ligase for CIP2A ubiquitination not identified
    • Stoichiometry of CIP2A within mTORC1 unresolved
  5. 2017 High

    Provided the structural basis for PP2A engagement: a crystal structure of the N-terminal fragment showed CIP2A homodimerizes and that dimerization is required for B56α/γ binding and CIP2A stability.

    Evidence Yeast two-hybrid, 3.0 Å crystal structure, structure-based mutagenesis, Co-IP

    PMID:28174209

    Open questions at the time
    • Structure covered only residues 1-560
    • Did not capture the assembled PP2A-CIP2A complex
  6. 2021 High

    Defined the mitotic DNA-lesion function and a therapeutic vulnerability, showing CIP2A localizes to DNA lesions in mitosis with TOPBP1 and is synthetically lethal in BRCA-deficient cells through prevention of acentric chromosome mis-segregation.

    Evidence Genome-scale CRISPR synthetic-lethality screens, live imaging, Co-IP, chromosome segregation assays

    PMID:34145035 PMID:35121901

    Open questions at the time
    • Mechanism by which CIP2A senses or marks mitotic lesions unresolved
    • Direct chromatin recruitment determinants not mapped
  7. 2022 High

    Clarified spatiotemporal control of the lesion complex, showing CIP2A is actively exported from interphase nuclei and only accesses chromatin at nuclear envelope breakdown to assemble with MDC1 and TOPBP1 at mitotic double-strand breaks.

    Evidence Co-IP, live imaging, fractionation, nuclear export inhibition, foci quantification

    PMID:35842428

    Open questions at the time
    • Nuclear export signal/receptor not defined
    • Order of assembly among CIP2A, MDC1, TOPBP1 unresolved
  8. 2023 High

    Delivered the molecular mechanism of PP2A inhibition, showing CIP2A displaces the PP2A-A subunit to form a pseudotrimer and blocks the B56α substrate pocket, validated by CRISPR head-domain mutagenesis abrogating tumor growth.

    Evidence Structural biology, CRISPR single-residue mutagenesis, phosphatase assays, xenograft

    PMID:36854761

    Open questions at the time
    • Generality of pseudotrimer model to other B56 isoforms not fully tested
    • Did not address PP2A-independent functions
  9. 2024 High

    Identified a metabolic role, showing CIP2A directly binds PKM2 to drive its tetramerization and mitochondrial relocalization, promoting oxidative phosphorylation in NSCLC.

    Evidence Co-IP, tetramer formation assays, PKM2-S287 mutagenesis, fractionation, in vivo metabolic assays

    PMID:38321019

    Open questions at the time
    • Single lab
    • Kinase responsible for PKM2-S287 and Bcl2-T69 phosphorylation not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CIP2A's distinct activities—PP2A pseudotrimer formation, Plk1 stabilization, mitotic TOPBP1 recruitment, and PKM2 tetramerization—are coordinated or partitioned across the cell cycle and tissue contexts.
  • No structure of the full-length protein or of the mitotic CIP2A-TOPBP1-MDC1 complex
  • Mechanism switching CIP2A between PP2A-dependent and PP2A-independent modes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 1
Partners
CTNNB1HRASMDC1MYCPKM2PLK1PPP2R5ATOPBP1
Complex memberships
CIP2A-B56α-PP2Ac pseudotrimerCIP2A-TOPBP1-MDC1 mitotic complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CIP2A directly interacts with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. Overexpression of CIP2A transforms human cells, demonstrating direct oncogenic activity. Direct interaction shown by co-immunoprecipitation; PP2A activity assays; cell transformation assays; in vivo tumor formation Cell High 17632056
2017 CIP2A forms homodimers, as confirmed by crystal structure of the N-terminal fragment (amino acids 1-560) at 3.0 Å resolution and structure-based mutational analyses. The CIP2A dimer interacts with PP2A subunits B56α and B56γ via a conserved N-terminal region; dimerization promotes B56 binding. Inhibition of either CIP2A dimerization or B56α/γ expression destabilizes CIP2A. Yeast two-hybrid, crystal structure determination, structure-based mutagenesis, co-immunoprecipitation validation EMBO reports High 28174209
2023 CIP2A inhibits PP2A-B56α by displacing the PP2A-A subunit and hijacking both B56α and the catalytic PP2Ac subunit to form a CIP2A-B56α-PP2Ac pseudotrimer. CIP2A also competes with B56α substrates by blocking the LxxIxE-motif substrate binding pocket on B56α. The N-terminal head domain mediates interaction with B56α and stabilizes CIP2A protein. CRISPR/Cas9 single amino acid mutagenesis of the head domain blunted MYC expression and MEK phosphorylation and abrogated triple-negative breast cancer tumor growth in vivo. Structural biology, CRISPR/Cas9 mutagenesis, phosphatase activity assays, in vivo xenograft tumor model Nature communications High 36854761
2021 CIP2A is cytoplasmic during interphase but accumulates at DNA lesions in mitosis as part of a complex with TOPBP1. CIP2A deficiency does not cause replication-associated DNA lesions but leads to lethal mis-segregation of acentric chromosomes in BRCA-deficient cells. Physical disruption of the CIP2A-TOPBP1 complex is highly deleterious in BRCA-deficient tumors, establishing CIP2A as a synthetic lethal target in BRCA1/2-mutated cancers. Genome-scale CRISPR-Cas9 synthetic lethality screens in isogenic BRCA1/2-deficient cells, live-cell imaging, co-immunoprecipitation, functional chromosome segregation assays Nature cancer High 35121901
2022 CIP2A is actively exported from the cell nucleus during interphase but, upon nuclear envelope breakdown at mitosis onset, gains access to chromatin where it forms a complex with MDC1 and TOPBP1 to promote TOPBP1 recruitment to sites of mitotic DNA double-strand breaks. Loss of CIP2A causes increased radio-sensitivity, micronuclei formation, and chromosomal instability. Co-immunoprecipitation, live-cell imaging, subcellular fractionation, nuclear export inhibition experiments, gamma-H2AX/TOPBP1 foci quantification Nature communications High 35842428
2014 CIP2A associates with mTORC1 and acts as an allosteric inhibitor of mTORC1-associated PP2A, enhancing mTORC1-dependent growth signaling and inhibiting autophagy. Under nutrient deprivation, CIP2A undergoes ubiquitination and p62/SQSTM1-dependent autophagic degradation, which reverses mTORC1 activation and destabilizes c-Myc. RNAi screen, co-immunoprecipitation (CIP2A-mTORC1 association), PP2A activity assays, autophagy flux assays, ubiquitination assays The Journal of cell biology High 24590173
2013 CIP2A translocates from the cytoplasm to the nucleus at mitotic entry, enriching at spindle poles. CIP2A directly interacts with the polo-box domain of Plk1 during mitosis, maintaining Plk1 stability by blocking APC/C-Cdh1-dependent proteolysis and enhancing Plk1 kinase activity. CIP2A depletion delays mitotic progression and causes mitotic abnormalities independently of PP2A activity. Subcellular fractionation and immunofluorescence (localization), co-immunoprecipitation (CIP2A-Plk1 interaction), Plk1 kinase activity assays, APC/C-Cdh1 ubiquitination assays, siRNA depletion with mitotic phenotype readout Cancer research High 23983103
2019 A micropeptide CIP2A-BP encoded by LINC00665 directly binds CIP2A and replaces the PP2A B56γ subunit, thereby releasing PP2A activity, which inhibits the PI3K/AKT/NFκB pathway and decreases expression of MMP-2, MMP-9, and Snail. TGF-β suppresses CIP2A-BP translation via Smad-induced 4E-BP1 upregulation. Co-immunoprecipitation (CIP2A-BP with CIP2A and B56γ), PP2A activity assays, Western blot, in vivo MMTV-PyMT model with CIP2A-BP gene introduction or direct peptide injection The EMBO journal High 31755573
2014 CIP2A physically associates with H-Ras in cervical cancer cells, leading to activation of the MEK/ERK signaling pathway and promoting epithelial-to-mesenchymal transition (EMT) and cervical cancer progression. Pull-down assay, mass spectrometry peptide sequencing, bilateral co-immunoprecipitation Cancer letters Medium 25458953
2010 CIP2A negatively regulates Akt-related PP2A activity in hepatocellular carcinoma cells; ectopic expression of CIP2A decreased Akt-related PP2A activity and upregulated phospho-Akt, while silencing CIP2A increased PP2A activity toward Akt. siRNA knockdown, CIP2A overexpression, PP2A phosphatase activity assays specific to Akt substrate, Western blot, in vivo xenograft Oncogene Medium 20729919
2018 CIP2A overexpression in neurons causes PP2A inhibition, driving tau/APP hyperphosphorylation at multiple sites, increased APP β-cleavage and Aβ production, tau mislocalization to dendrites and spines, synaptic degeneration, and cognitive deficits. AAV-CIP2A hippocampal injection in mice induced AD-like cognitive deficits and impaired LTP. AAV-mediated CIP2A overexpression in mouse hippocampus, PP2A activity assays, Western blot for phospho-tau/APP, LTP electrophysiology, behavioral cognitive assays Cell reports High 30021167
2022 Chk1 activity is elevated in AD brains and Chk1 overexpression induces CIP2A upregulation, PP2A inhibition, tau and APP hyperphosphorylation, synaptic impairments, and cognitive memory deficit in mice. Chk1 inhibition decreases CIP2A expression and restores PP2A activity. AAV-GFAP-ChK1 in vivo brain injection, Chk1 inhibitor (GDC0575) treatment in AD cell models and APP/PS1 mice, Western blot, PP2A activity assays, behavioral tests Neurotherapeutics Medium 35286657
2009 H. pylori CagA protein upregulates CIP2A expression in gastric cells via the Src and MEK/ERK (Ras/MEK/ERK) signaling pathways, and CIP2A upregulation is dependent on CagA phosphorylation. CIP2A depletion partially attenuated H. pylori infection-induced Myc stabilization. Plasmid-mediated CagA expression in gastric cell lines, H. pylori infection, signal inhibitors (Src inhibitor, MEK inhibitor), immunoblotting, CIP2A siRNA depletion Journal of medical microbiology Medium 19959630
2012 CIP2A depletion inhibits JNK2 expression and transwell migration independently of MYC, whereas MYC depletion does not affect JNK2 expression or migration. PP2A inhibition reverses CIP2A siRNA-elicited inhibition of colony growth and activation of MYC-repressed genes. siRNA depletion of CIP2A vs. MYC, JNK2 expression analysis, transwell migration assay, PP2A inhibitor rescue experiment Oncogene Medium 22249265
2016 CIP2A promotes primary cilia disassembly through activation of Aurora A kinase; CIP2A depletion increases ciliated cell frequency and cilia length. CIP2A is localized in the centrosome. CIP2A depletion also shifts cellular metabolism toward the glycolytic pathway independently of cilia assembly. Immunofluorescence localization, CIP2A overexpression and siRNA depletion, Aurora A kinase activity measurement, cilia length quantification, glycolysis metabolic assays EMBO reports Medium 29491003
2024 CIP2A binds to PKM2 and induces PKM2 tetramer formation, with serine 287 identified as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirects PKM2 to the mitochondrion, leading to Bcl2 upregulation via phosphorylation of Bcl2 at threonine 69, thereby promoting oxidative phosphorylation and inhibiting glycolysis in NSCLC cells. Co-immunoprecipitation (CIP2A-PKM2 interaction), biochemical tetramer formation assays, site-directed mutagenesis of PKM2-S287, subcellular fractionation, Western blot for Bcl2-T69 phosphorylation, in vitro and in vivo metabolic assays Cell discovery High 38321019
2012 In spermatogonial progenitor cells, CIP2A is co-expressed with PLZF and ki-67. CIP2A mutant mice show reduced PLZF-positive spermatogonial progenitor cell numbers and reduced sperm counts. Spermatogonia-specific restoration of CIP2A expression rescues PLZF expression and sperm production defects, establishing a physiological role for CIP2A in maintaining spermatogonial progenitor cells upstream of PLZF. CIP2A mutant mouse model, genetic rescue with spermatogonia-specific CIP2A re-expression, qRT-PCR for Plzf/Oct-4/Nanog, sperm count, PLZF IHC PloS one Medium 22461891
2016 CIP2A promotes T-cell activation during adaptive immune response; CIP2A-deficient mice show decreased frequency of CD4+ and CD8+ effector T-cells upon Listeria monocytogenes infection. CIP2A expression is induced during T-cell activation in a Zap70 activity-dependent manner. CIP2A-deficient mouse (CIP2AHOZ) model, Listeria infection challenge, T-cell frequency analysis by flow cytometry, Zap70 inhibitor treatment, cell-autonomous T-cell activation assay PloS one Medium 27100879
2020 CIP2A negatively regulates IL-17 production by Th17 cells; CIP2A-deficient Th17 cells show increased strength and duration of STAT3 phosphorylation. CIP2A regulates the strength of interaction between AGK (Acylglycerol Kinase) and STAT3, thereby modulating STAT3 phosphorylation and IL-17 expression. CIP2A-deficient mouse/human Th17 differentiation assays, phospho-STAT3 measurement, phospho-STAT3 interactome analysis by MS, genome-wide gene expression profiling, co-immunoprecipitation of AGK-STAT3 iScience Medium 32171124
2021 CIP2A directly interacts with TopBP1 (a DNA repair scaffold protein) and this interaction is required for DNA damage-induced mitotic checkpoint function and survival of HR-defective BLBC cells. CIP2A inhibition results in enhanced DNA damage-induced TopBP1 and RAD51 recruitment to chromatin in mammary epithelial cells. CIP2A drives MYC and E2F1 proliferative signaling in basal-like TNBC cells. Co-immunoprecipitation (CIP2A-TopBP1 direct interaction), CRISPR/Cas9 CIP2A knockout in isogenic cell pairs, chromatin fractionation for TopBP1/RAD51, BLBC mouse tumor initiation model, patient-derived xenograft Cancer research High 34145035
2023 In meiosis I oocytes, CIP2A forms a complex with MDC1 and TOPBP1 at spindle poles; upon DSB induction, the CIP2A-MDC1-TOPBP1 complex is transported from spindle poles to chromosomes via microtubules (kinetochore/centromere as structural hub). This transport requires CENP-A and HEC1 and is regulated by PLK1 but not ATM. This mechanism allows oocytes to repair DSBs during meiosis. Immunofluorescence imaging, microtubule depolymerization experiments, CIP2A depletion (p-MDC1 and p-TOPBP1 recruitment assay), CENP-A/HEC1 depletion, PLK1 and ATM inhibition Nucleic acids research Medium 36999590
2021 A CIP2A splicing variant called NOCIVA (novel CIP2A variant) contains CIP2A exons 1-13 fused to 349 nucleotides from CIP2A intron 13 encoding a unique 13-amino acid tail. NOCIVA retains capacity to bind B56α but, unlike cytoplasmic CIP2A, translocates to the nucleus. NOCIVA overexpression is characteristic of myeloid malignancies and predicts tyrosine kinase inhibitor resistance in CML. 5' and 3' RACE for variant characterization, structural and molecular biology binding assays, nuclear/cytoplasmic fractionation, clinical cohort analysis for TKI resistance Clinical cancer research Medium 33674272
2016 CIP2A promotes p27Kip1 phosphorylation at Ser10 via inhibiting Akt-associated PP2A activity, causing p27Kip1 cytoplasmic relocalization and degradation. CIP2A also recruits c-Myc to mediate transcriptional inhibition of p27Kip1, resulting in cell cycle progression in TNBC cells. CIP2A siRNA knockdown, CIP2A overexpression, PP2A activity assay, Western blot for p27Kip1-Ser10 phosphorylation, nuclear/cytoplasmic fractionation, ChIP for c-Myc at p27Kip1 promoter, xenograft growth Oncogene Medium 27694903
2017 CIP2A mediates fibronectin-induced bladder cancer cell proliferation by stabilizing β-catenin. CIP2A physically interacts with β-catenin (confirmed by co-immunoprecipitation and immunofluorescence co-localization), and this interaction enhances β-catenin stability and FN-induced proliferation. Co-immunoprecipitation, immunofluorescence co-localization, cycloheximide chase assay for β-catenin stability, CIP2A siRNA depletion, in vivo xenograft Journal of experimental & clinical cancer research Medium 28521777
2016 HDAC1 controls CIP2A transcription; HDAC1 inhibition by a small molecule or specific siRNA downregulates CIP2A transcription in colorectal cancer cells, restoring PP2A activity, which dephosphorylates pGSK-3β(Ser9), leading to β-catenin phosphorylation, cytosolic retention, degradation, and decreased c-Myc/cyclin D1 expression. HDAC1 siRNA, pharmacological HDAC1 inhibitor, CIP2A mRNA/protein measurement, PP2A activity assay, β-catenin phosphorylation Western blot, in vivo xenograft Oncotarget Medium 27029072
2015 Oct4 positively regulates CIP2A expression in testicular cancer cell lines and embryonic stem cells; Oct4 and CIP2A are co-expressed in CD24-positive side-population of patient-derived HNSCC cell lines and cooperate in radioresistance. Oct4 overexpression/knockdown with CIP2A mRNA/protein measurement, luciferase reporter assays, cell line radioresistance assays Oncotarget Low 25474139
2018 HOXB13 protein binds to the CIP2A gene locus (chromatin binding demonstrated) and functionally promotes CIP2A transcription; ectopic expression of HOXB13 stimulates prostate cancer cell growth and migration in a CIP2A-dependent manner. ChIP assay showing HOXB13 chromatin binding at CIP2A locus, CIP2A mRNA/protein measurement after HOXB13 overexpression, functional cell growth/migration assays Clinical cancer research Medium 30181389
2014 Estradiol increases CIP2A expression at the translational level in a c-MYC-independent manner via EGFR activation of MAPK and PI3K pathways converging on p70 S6 kinase (S6K), which phosphorylates eIF4B to increase CIP2A translation. Pharmacological inhibitors of EGFR, MEK, PI3K, and S6K; eIF4B phosphorylation Western blot; polysome profiling (translational regulation); cycloheximide chase; siRNA knockdown of S6K Endocrine-related cancer Medium 24280132
2016 Lapatinib inhibits CIP2A transcription by disturbing the binding of Elk1 to the CIP2A promoter, and an erlotinib derivative TD52 also downregulates CIP2A transcription via Elk1; these transcription factor-CIP2A promoter interactions mediate drug-induced apoptosis through the CIP2A/PP2A/Akt axis. ChIP assay for Elk1 binding to CIP2A promoter, CIP2A mRNA measurement, PP2A activity assay, in vivo xenograft Oncotarget / European journal of cancer Medium 26824320 28027514
2022 TP53TG1 lncRNA interacts with CIP2A protein and triggers its ubiquitination-mediated degradation, resulting in inhibition of the PI3K/AKT pathway. Co-immunoprecipitation (TP53TG1-CIP2A interaction), ubiquitination assay, CIP2A protein stability assay, Western blot for AKT signaling Cancer science Low 36114757
2016 CHK1 overexpression/constitutive activity positively regulates CIP2A gene expression, and pSTAT3 and CIP2A form a recursively wired transcriptional circuit in glioblastoma; perturbing CIP2A expression induces GBM cell senescence and retards tumor growth in vitro and in vivo. siRNA and pharmacological CHK1 inhibitors with CIP2A mRNA/protein measurement, pSTAT3 inhibition, luciferase reporter assays, in vivo GBM model Molecular cancer research Medium 32079743
2018 MycN and CIP2A are co-expressed in the neural plate but excluded from the adjacent neural crest domain; ectopic expression of either MycN or CIP2A in the neural crest biases cells toward CNS-like neural stem cells expressing Sox2, suggesting a cell-fate regulatory function for CIP2A. In ovo electroporation of CIP2A and MycN in chick neural crest, immunofluorescence for neural identity markers (Sox2), lineage tracing PNAS Medium 30021854
2016 CIP2A promotes multidrug resistance in cervical adenocarcinoma by enhancing P-glycoprotein (P-gp) expression through the transcription factor E2F1; CIP2A knockdown decreases P-gp expression at the transcriptional level and reduces P-gp efflux activity. CIP2A siRNA and overexpression, P-gp expression (Western blot, RT-PCR), Rhodamine 123 efflux assay for P-gp activity, E2F1 regulation analysis, drug sensitivity assays Tumour biology Low 26404133
2024 SFXN1 (sideroflexin-1) promotes TNBC progression by inhibiting the autophagy receptor TOLLIP-mediated autophagic degradation of CIP2A, thereby maintaining CIP2A protein levels and activating the CIP2A/PP2A/p-AKT pathway. Label-free quantitative proteomics/LC-MS to identify SFXN1 targets, immunoblotting for CIP2A autophagy flux, immunofluorescence for co-localization, RT-qPCR, in vitro and in vivo functional assays Cancer letters Low 38849012

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 CIP2A inhibits PP2A in human malignancies. Cell 536 17632056
2019 Micropeptide CIP2A-BP encoded by LINC00665 inhibits triple-negative breast cancer progression. The EMBO journal 207 31755573
2009 CIP2A is associated with human breast cancer aggressivity. Clinical cancer research : an official journal of the American Association for Cancer Research 198 19671842
2010 CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells. Oncogene 142 20729919
2008 CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clinical cancer research : an official journal of the American Association for Cancer Research 130 18559589
2012 CIP2A is a target of bortezomib in human triple negative breast cancer cells. Breast cancer research : BCR 114 22537901
2022 m6A modification-mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability. Cancer science 107 36114757
2021 The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer. Nature cancer 93 35121901
2017 Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56. EMBO reports 88 28174209
2011 Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer. PloS one 83 21655278
2010 CIP2A expression is increased in prostate cancer. Journal of experimental & clinical cancer research : CR 82 20964854
2018 CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer's Disease. Cell reports 81 30021167
2013 CIP2A modulates cell-cycle progression in human cancer cells by regulating the stability and activity of Plk1. Cancer research 66 23983103
2012 CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes. Oncogene 66 22249265
2014 Oncogenic nexus of cancerous inhibitor of protein phosphatase 2A (CIP2A): an oncoprotein with many hands. Oncotarget 64 25015035
2014 CIP2A oncoprotein controls cell growth and autophagy through mTORC1 activation. The Journal of cell biology 63 24590173
2012 CIP2A-mediated Akt activation plays a role in bortezomib-induced apoptosis in head and neck squamous cell carcinoma cells. Oral oncology 59 22342571
2017 The role of CIP2A in cancer: A review and update. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 58 29035828
2012 CIP2A overexpression is associated with c-Myc expression in colorectal cancer. Cancer biology & therapy 56 22310977
2021 SP1-induced lncRNA DUBR promotes stemness and oxaliplatin resistance of hepatocellular carcinoma via E2F1-CIP2A feedback. Cancer letters 55 34958891
2011 CIP2A is over-expressed in acute myeloid leukaemia and associated with HL60 cells proliferation and differentiation. International journal of laboratory hematology 55 21219591
2011 Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients' survival. British journal of cancer 55 22075943
2020 Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1. The Journal of biological chemistry 51 32071079
2012 CIP2A promotes proliferation of spermatogonial progenitor cells and spermatogenesis in mice. PloS one 51 22461891
2022 The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis. Nature communications 50 35842428
2016 Lapatinib inhibits CIP2A/PP2A/p-Akt signaling and induces apoptosis in triple negative breast cancer cells. Oncotarget 50 26824320
2011 Increase in CIP2A expression is associated with doxorubicin resistance. FEBS letters 50 21241697
2019 Cucurbitacin B Induces the Lysosomal Degradation of EGFR and Suppresses the CIP2A/PP2A/Akt Signaling Axis in Gefitinib-Resistant Non-Small Cell Lung Cancer. Molecules (Basel, Switzerland) 48 30759826
2012 Inhibition of CIP2A determines erlotinib-induced apoptosis in hepatocellular carcinoma. Biochemical pharmacology 46 23178652
2015 CIP2A is an Oct4 target gene involved in head and neck squamous cell cancer oncogenicity and radioresistance. Oncotarget 45 25474139
2014 CIP2A cooperates with H-Ras to promote epithelial-mesenchymal transition in cervical-cancer progression. Cancer letters 45 25458953
2010 CIP2A expression and localization in oral carcinoma and dysplasia. Cancer biology & therapy 43 21068540
2010 CIP2A is overexpressed in esophageal squamous cell carcinoma. Medical oncology (Northwood, London, England) 43 21140243
2018 Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer. International journal of oncology 42 29956727
2018 Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma. Proceedings of the National Academy of Sciences of the United States of America 40 30021854
2024 CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer. Cell discovery 39 38321019
2021 CIP2A Interacts with TopBP1 and Drives Basal-Like Breast Cancer Tumorigenesis. Cancer research 39 34145035
2016 EGFR-independent Elk1/CIP2A signalling mediates apoptotic effect of an erlotinib derivative TD52 in triple-negative breast cancer cells. European journal of cancer (Oxford, England : 1990) 38 28027514
2013 Ethoxysanguinarine Induces Inhibitory Effects and Downregulates CIP2A in Lung Cancer Cells. ACS medicinal chemistry letters 38 24900782
2009 Helicobacter pylori CagA upregulation of CIP2A is dependent on the Src and MEK/ERK pathways. Journal of medical microbiology 38 19959630
2013 CIP2A influences survival in colon cancer and is critical for maintaining Myc expression. PloS one 35 24098375
2012 CIP2A is overexpressed in human ovarian cancer and regulates cell proliferation and apoptosis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 22923389
2014 CIP2A mediates erlotinib-induced apoptosis in non-small cell lung cancer cells without EGFR mutation. Lung cancer (Amsterdam, Netherlands) 34 24954871
2012 CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma. Medical oncology (Northwood, London, England) 33 23275123
2023 Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A. Nature communications 32 36854761
2019 Inhibitory effects of polyphyllins I and VII on human cisplatin-resistant NSCLC via p53 upregulation and CIP2A/AKT/mTOR signaling axis inhibition. Chinese journal of natural medicines 32 31703757
2018 The concept of the okadaic acid class of tumor promoters is revived in endogenous protein inhibitors of protein phosphatase 2A, SET and CIP2A, in human cancers. Journal of cancer research and clinical oncology 31 30341686
2017 Celastrol inhibits chondrosarcoma proliferation, migration and invasion through suppression CIP2A/c-MYC signaling pathway. Journal of pharmacological sciences 31 28522217
2017 Antihelminthic drug niclosamide inhibits CIP2A and reactivates tumor suppressor protein phosphatase 2A in non-small cell lung cancer cells. Biochemical pharmacology 31 28813646
2014 TD-19, an erlotinib derivative, induces epidermal growth factor receptor wild-type nonsmall-cell lung cancer apoptosis through CIP2A-mediated pathway. The Journal of pharmacology and experimental therapeutics 30 25187431
2014 CIP2A regulates cell proliferation via the AKT signaling pathway in human lung cancer. Oncology reports 28 25109354
2010 CIP2A increases self-renewal and is linked to Myc in neural progenitor cells. Differentiation; research in biological diversity 28 20447748
2018 Chronic Cigarette Smoke Exposure Subdues PP2A Activity by Enhancing Expression of the Oncogene CIP2A. American journal of respiratory cell and molecular biology 26 30011381
2017 Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A. Oncology reports 26 28560452
2010 CIP2A expression is elevated in cervical cancer. Cancer biomarkers : section A of Disease markers 26 22072119
2022 Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 25 35286657
2018 CIP2A Promotes Proliferation, Invasion and Chemoresistance to Cisplatin in Renal Cell Carcinoma. Journal of Cancer 25 30410608
2015 CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations. Oncotarget 24 25965834
2014 KIAA1524/CIP2A promotes cancer growth by coordinating the activities of MTORC1 and MYC. Autophagy 24 24905455
2017 CIP2A mediates fibronectin-induced bladder cancer cell proliferation by stabilizing β-catenin. Journal of experimental & clinical cancer research : CR 23 28521777
2015 CIP2A overexpression induces autoimmune response and enhances JNK signaling pathway in human lung cancer. BMC cancer 22 26560124
2013 CIP2A is overexpressed in osteosarcoma and regulates cell proliferation and invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 24014087
2019 Cip2a/miR-301a feedback loop promotes cell proliferation and invasion of triple-negative breast cancer. Journal of Cancer 21 31762806
2018 Cucurbitacin B induces inhibitory effects via CIP2A/PP2A/Akt pathway in glioblastoma multiforme. Molecular carcinogenesis 21 29393542
2018 CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits. Neurobiology of aging 21 30594047
2023 CIP2A coordinates phosphosignaling, mitosis, and the DNA damage response. Trends in cancer 20 37793965
2018 Synergistic Interaction of HOXB13 and CIP2A Predisposes to Aggressive Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 20 30181389
2023 Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes. Nucleic acids research 19 36999590
2022 Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma. Frontiers in genetics 18 35350239
2016 Cross Talk between Wnt/β-Catenin and CIP2A/Plk1 Signaling in Prostate Cancer: Promising Therapeutic Implications. Molecular and cellular biology 18 27090640
2016 CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection. PloS one 18 27100879
2016 Cip2a promotes cell cycle progression in triple-negative breast cancer cells by regulating the expression and nuclear export of p27Kip1. Oncogene 18 27694903
2015 Role of "oncogenic nexus" of CIP2A in breast oncogenesis: how does it work? American journal of cancer research 18 26609493
2014 Expression patterns of microRNA-218 and its potential functions by targeting CIP2A and BMI1 genes in melanoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 24839010
2013 Expression and biological role of CIP2A in human astrocytoma. Molecular medicine reports 18 23467938
2022 ChK1 activation induces reactive astrogliosis through CIP2A/PP2A/STAT3 pathway in Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 35195302
2020 Constitutive CHK1 Expression Drives a pSTAT3-CIP2A Circuit that Promotes Glioblastoma Cell Survival and Growth. Molecular cancer research : MCR 17 32079743
2010 KIAA1524: A novel MLL translocation partner in acute myeloid leukemia. Leukemia research 17 20943269
2018 CIP2A facilitates the G1/S cell cycle transition via B-Myb in human papillomavirus 16 oncoprotein E6-expressing cells. Journal of cellular and molecular medicine 16 29893470
2016 Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents. Oncology reports 16 27779687
2014 Estradiol enhances CIP2A expression by the activation of p70 S6 kinase. Endocrine-related cancer 16 24280132
2014 Role of CIP2A in the antitumor effect of bortezomib in colon cancer. Molecular medicine reports 16 24789441
2020 Effect of CIP2A and its mechanism of action in the malignant biological behavior of colorectal cancer. Cell communication and signaling : CCS 15 32321509
2018 Euxanthone suppresses tumor growth and metastasis in colorectal cancer via targeting CIP2A/PP2A pathway. Life sciences 15 30144452
2016 CIP2A down regulation enhances the sensitivity of pancreatic cancer cells to gemcitabine. Oncotarget 15 26894380
2014 CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer. Molecular bioSystems 15 25325377
2020 CIP2A Constrains Th17 Differentiation by Modulating STAT3 Signaling. iScience 14 32171124
2018 miR-548b-3p Regulates Proliferation, Apoptosis, and Mitochondrial Function by Targeting CIP2A in Hepatocellular Carcinoma. BioMed research international 14 30671469
2024 Sideroflexin-1 promotes progression and sensitivity to lapatinib in triple-negative breast cancer by inhibiting TOLLIP-mediated autophagic degradation of CIP2A. Cancer letters 13 38849012
2021 2,5-Dimethyl Celecoxib Inhibits Proliferation and Cell Cycle and Induces Apoptosis in Glioblastoma by Suppressing CIP2A/PP2A/Akt Signaling Axis. Journal of molecular neuroscience : MN 13 33400072
2021 Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias. Clinical cancer research : an official journal of the American Association for Cancer Research 13 33674272
2020 Polyphyllin I attenuates cognitive impairments and reduces AD-like pathology through CIP2A-PP2A signaling pathway in 3XTg-AD mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 33070372
2019 Genistein Decreases APP/tau Phosphorylation and Ameliorates Aβ Overproduction Through Inhibiting CIP2A. Current Alzheimer research 13 31470788
2015 CIP2A is associated with multidrug resistance in cervical adenocarcinoma by a P-glycoprotein pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 26404133
2011 CIP2A expression is associated with synovial hyperplasia and invasive function of fibroblast-like synoviocytes in rheumatoid arthritis. Rheumatology international 13 21479604
2019 Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia. Cancers 12 31717978
2018 Protein phosphatase 2A (PP2A) inhibitor CIP2A indicates resistance to radiotherapy in rectal cancer. Cancer medicine 12 29441695
2018 Oncoprotein CIP2A promotes the disassembly of primary cilia and inhibits glycolytic metabolism. EMBO reports 12 29491003
2017 CIP2A is overexpressed in human endometrioid adenocarcinoma and regulates cell proliferation, invasion and apoptosis. Pathology, research and practice 12 29274810
2016 HDAC1 controls CIP2A transcription in human colorectal cancer cells. Oncotarget 12 27029072

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