Affinage

Showing CDKN1B — P27KIP1 is a alias.

CDKN1B

Cyclin-dependent kinase inhibitor 1B · UniProt P46527

Length
198 aa
Mass
22.1 kDa
Annotated
2026-06-09
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

p27(Kip1)/CDKN1B is a CDK inhibitor that enforces cell cycle arrest by binding cyclin/CDK complexes, and it functions as a tumor suppressor whose loss drives hyperproliferation, pituitary tumors, and gigantism (PMID:15950907, PMID:25486569). Its inhibitory activity is set by the abundance and stoichiometry of its targets: Myc-induced cyclins D1/D2 sequester p27 to release cyclin E–CDK2, while pRb drives posttranscriptional accumulation of cyclin E-bound p27 to enforce senescence (PMID:10508164, PMID:11340156). p27 inhibits cyclin D–CDK4 with nanomolar potency, and this inhibition is relieved through sequential tyrosine phosphorylation—Abl phosphorylates Tyr88, enabling Src-mediated Tyr74 modification that partially reactivates CDK4 within ternary complexes—a mechanism co-opted oncogenically by FLT3/FLT3-ITD, which phosphorylates Tyr88 to inactivate p27 in AML (PMID:22276948, PMID:28522571). p27 abundance is controlled at every level: transcriptionally it is induced by the Ah receptor and by BRCA1/FOXA1, and repressed by Myc, AP-1, and MLL-AF4 (PMID:10398686, PMID:16331276, PMID:11313917, PMID:19959471, PMID:16169901); its mRNA is stabilized by QKI RNA-binding proteins (PMID:15568022); and its protein stability is governed by phosphorylation (CK2α', and a steric/phospho switch at T198 reversed by the phosphatase PPM1G) and by degradation routes including Skp2 downstream of FAK, COP1/CSN6, BAP31, nucleolar polyubiquitylation by nucleostemin, and selective autophagy via the SQSTM1/p62 receptor (PMID:18311148, PMID:21423803, PMID:27822412, PMID:16705171, PMID:25945542, PMID:30338855, PMID:27998760, PMID:26569626). Beyond cyclin/CDK inhibition, p27 arrests the cycle independently of CDK2 and executes CDK-independent functions: cytoplasmic p27 promotes motility, invasion, and survival by downregulating RhoA, modulating Akt stability, and bridging Cortactin to PAK1 at invadopodia, and it controls cytokinesis by binding citron kinase to block its activation by RhoA (PMID:15950907, PMID:16489017, PMID:28287395, PMID:22293177). Nuclear p27 acts as a transcriptional co-repressor, associating with the Sox2 SRR2 enhancer in a p130-E2F4-SIN3A complex (PMID:23217425). p27 also cooperates with p57 to retain Hsc70/cyclin D1 in the cytoplasm to maintain hematopoietic stem cell quiescence, and stabilizes ATAT1 to support tubulin acetylation and axonal transport (PMID:21885020, PMID:29791853).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Establishing how mitogenic Myc overcomes p27 inhibition showed that cyclin D sequestration—not D-CDK kinase activity—redistributes CKIs to free cyclin E-CDK2, defining a stoichiometric titration model of cell cycle entry.

    Evidence Cyclin D1/D2 knockout MEFs with kinase-dead complementation and co-IP

    PMID:10508164

    Open questions at the time
    • Does not quantify endogenous p27 redistribution kinetics
    • Does not address other CKI targets
  2. 1999 High

    Linking p27 to an environmental signaling receptor, AhR was shown to directly induce p27 transcription to mediate dioxin-induced growth arrest, broadening p27 regulation beyond intrinsic mitogen pathways.

    Evidence Antisense p27 and Kip1-knockout mouse tissue with transcription assays

    PMID:10398686

    Open questions at the time
    • Direct AhR binding to the p27 promoter not mapped
    • Tissue specificity beyond thymus unaddressed
  3. 2001 Medium

    Identifying transcriptional repressors of p27 explained mitogen-driven downregulation: Myc represses the p27 promoter via box II and an Inr element with Max, while pRb conversely drives posttranscriptional accumulation of cyclin E-bound p27 to enforce senescence.

    Evidence Promoter-luciferase/deletion analysis and pRb reintroduction with antisense knockdown

    PMID:11313917 PMID:11340156

    Open questions at the time
    • Repression mechanism is reporter-based, not endogenous chromatin
    • pRb-to-p27 posttranscriptional link not molecularly defined
  4. 2002 High

    Defining the kinase for S10 phosphorylation, hKIS was shown to bind p27's C-terminus and phosphorylate S10 to promote nuclear export, establishing localization control as a regulatory layer.

    Evidence In vitro kinase assay, co-IP, and siRNA depletion with cell cycle analysis

    PMID:12093740

    Open questions at the time
    • Structural basis of C-terminal binding unresolved
    • Crosstalk with degradation pathways not addressed
  5. 2004 High

    Demonstrating mRNA-level control, QKI RNA-binding proteins were found to bind and stabilize p27 mRNA to drive oligodendrocyte differentiation, adding post-transcriptional regulation to the p27 abundance circuit.

    Evidence RNA-IP, retroviral QKI expression, and mRNA stability assays in Qkv mutant mice

    PMID:15568022

    Open questions at the time
    • QKI binding site on p27 mRNA not mapped
    • Generality beyond oligodendrocytes unknown
  6. 2005 High

    Resolving whether p27's tumor-suppressive arrest required CDK2, genetic epistasis showed p27 inhibits the cycle and suppresses tumors independently of CDK2, decoupling p27 function from its canonical target.

    Evidence Cdk2-null MEFs, ectopic expression, and p27/Cdk2 double-knockout tumor analysis

    PMID:15950907

    Open questions at the time
    • Identity of the CDK2-independent effector not defined here
    • Does not exclude CDK1/other CDK redundancy
  7. 2006 Medium

    Uncovering CDK-independent oncogenic activity, cytoplasmic p27 was shown to downregulate RhoA, increase motility, and stabilize Akt to promote survival and tumorigenicity, reframing mislocalized p27 as oncogenic.

    Evidence p27deltaNLS mutant, RNAi, Akt turnover assays, and glioma xenografts

    PMID:16489017

    Open questions at the time
    • Direct molecular link between p27 and Akt stability unresolved
    • Single cell-type/xenograft model
  8. 2006 Medium

    Two transcriptional and stability inputs were mapped: BRCA1/FOXA1 synergistically activate the p27 promoter, while FAK sustains Skp2-dependent p27 degradation to permit endothelial proliferation and angiogenesis.

    Evidence Reporter assays, EMSA, and dominant-negative FAK with Skp2/p27 siRNA

    PMID:16331276 PMID:16705171

    Open questions at the time
    • Single-lab reporter/EMSA data for the activation arm
    • FAK-Skp2 link is indirect (mRNA level)
  9. 2008 High

    Identifying a tissue-specific stability circuit, CK2α' was shown to phosphorylate p27 for degradation in angiotensin II-stimulated cardiomyocytes, with unphosphorylated p27 inhibiting CK2α' in a feedback loop controlling hypertrophy.

    Evidence In vitro kinase assay, co-IP, proteasome inhibition, and CK2α' manipulation in cardiomyocytes

    PMID:18311148

    Open questions at the time
    • CK2α' target residue on p27 not specified
    • Relationship to other degradation routes unclear
  10. 2011 High

    Two stem/quiescence and stability mechanisms were defined: p27 and p57 cooperatively retain Hsc70/cyclin D1 in the cytoplasm to maintain HSC quiescence, while a steric T198 switch controls proteasomal stability and T198 phosphorylation governs stathmin binding and motility.

    Evidence Conditional double-knockout mice with fractionation/transplantation, and T198 mutants with proteasome and binding assays

    PMID:21423803 PMID:21885020

    Open questions at the time
    • Mechanism of Hsc70/cyclin D1 cytoplasmic retention by p27 incomplete
    • T198 conformational model based on mutants, not structure
  11. 2012 High

    CDK-independent and biochemical mechanisms were established: p27 binds citron kinase to block RhoA activation during cytokinesis, associates with the Sox2 SRR2 enhancer in a p130-E2F4-SIN3A repressor complex, and integrates sequential Abl/Src tyrosine phosphorylation to partially reactivate CDK4.

    Evidence p27CK- knock-in mice, ChIP with Sox2-haploinsufficiency epistasis, and in vitro reconstitution with ITC

    PMID:22276948 PMID:22293177 PMID:23217425

    Open questions at the time
    • In vivo prevalence of Y88/Y74 dual phosphorylation not quantified
    • Sox2 co-repressor assembly order incompletely defined
  12. 2013 Medium

    Extending the arrest function to terminal differentiation, p21/p27 were shown to bind cyclin E/A-CDK2 and be required for postnatal cardiomyocyte G1 cell cycle exit, with loss causing endoreplication.

    Evidence Co-IP of CDK complexes and p21/p27 knockout cardiomyocyte cell cycle profiling

    PMID:24380855

    Open questions at the time
    • Relative contribution of p27 vs p21 not separated
    • Single-lab study
  13. 2014 High

    Validating stathmin as a physiological partner, co-ablation of stathmin rescued most p27-null hyperproliferative phenotypes via restored CDK4/6 activity, establishing the p27-stathmin axis in G1/S control in vivo.

    Evidence p27/stathmin double-knockout mice with proliferation and CDK kinase assays

    PMID:25486569

    Open questions at the time
    • Molecular link between p27-stathmin and CDK4/6 activity indirect
    • Cytoplasmic vs nuclear contribution not separated
  14. 2016 Medium

    Multiple degradation and stability regulators were defined: CSN6/COP1 and nucleostemin (nucleolar polyubiquitylation) target p27 for proteasomal turnover, while PPM1G dephosphorylates T198 to stabilize p27 and block 14-3-3θ-mediated export.

    Evidence Co-IP, ubiquitination and phosphatase assays, fractionation, and CDK2 activity assays

    PMID:25945542 PMID:27822412 PMID:27998760

    Open questions at the time
    • E3 ligase hierarchy among COP1/Skp2/nucleostemin unresolved
    • Single-lab biochemistry for each route
  15. 2017 High

    Disease-relevant and cytoplasmic mechanisms were established: FLT3/FLT3-ITD directly phosphorylates p27 Y88 to inactivate it in AML, and cytoplasmic p27 bridges Cortactin to PAK1 to limit invadopodia turnover during invasion.

    Evidence In vitro phosphorylation with phospho-antibodies and inhibitor in patient AML samples; reciprocal co-IP with Cortactin phospho-mutants

    PMID:28287395 PMID:28522571

    Open questions at the time
    • Contribution of Y88 phosphorylation to clinical FLT3-ITD outcomes not quantified
    • Cortactin/PAK1 axis tested in limited cell contexts
  16. 2018 Medium

    A neuronal cytoskeletal role was uncovered: p27 stabilizes ATAT1 to promote α-tubulin acetylation and axonal transport, with Drosophila dacapo loss disrupting transport, extending p27 function to cytoskeletal regulation.

    Evidence Cortical neuron assays, ATAT1 stability measurements, and Drosophila dacapo knockdown

    PMID:29791853

    Open questions at the time
    • Mechanism of ATAT1 stabilization by p27 not defined
    • Mammalian in vivo confirmation limited
  17. 2019 Medium

    An additional degradation partner, BAP31, was shown to promote p27 proteasomal degradation, with an anti-BAP31 intrabody stabilizing p27 and suppressing gastric tumor growth.

    Evidence Co-IP, intrabody blocking, proteasome inhibition, and xenografts

    PMID:30338855

    Open questions at the time
    • E3 ligase mediating BAP31-dependent degradation unidentified
    • Single-lab and tumor-model specific

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many parallel degradation routes (Skp2, COP1/CSN6, BAP31, nucleostemin, autophagy/p62) and modification switches are integrated to set p27 levels and localization in a given cell context, and the structural basis of its disordered-domain conformational switching, remain unresolved.
  • No unified hierarchy of competing degradation pathways
  • No structural model linking T198/Y88 modifications to conformation
  • Context-dependence of nuclear vs cytoplasmic function not predictable

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 1
Partners
ATAT1CDK4CITRON KINASECTTNPAK1SKP2SQSTM1STATHMIN
Complex memberships
cyclin D-CDK4cyclin E-CDK2p130-E2F4-SIN3A repressor complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 hKIS (human kinase interacting stathmin) is the nuclear kinase responsible for phosphorylating p27(Kip1) on serine 10 (S10). hKIS binds the C-terminal domain of p27(Kip1) and phosphorylates it on S10 in vitro and in vivo, promoting its nuclear export to the cytoplasm. hKIS is activated by mitogens during G0/G1, and siRNA depletion of KIS inhibits S10 phosphorylation and enhances growth arrest. In vitro kinase assay, co-immunoprecipitation, siRNA knockdown, cell cycle analysis The EMBO journal High 12093740
1999 Cyclins D1 and D2, induced by Myc, sequester p27(Kip1) and p21(Cip1) into cyclin D-CDK complexes, thereby releasing cyclin E-CDK2 from inhibition and promoting cell cycle progression. Primary fibroblasts from cyclin D1(-/-) or cyclin D2(-/-) mice do not proliferate in response to Myc. A kinase-defective cyclin D1 mutant that still binds CKIs restores Myc sensitivity, demonstrating that the sequestration function—not kinase activity—is required. Genetic knockout mouse embryo fibroblasts, retroviral complementation with kinase-dead mutants, biochemical co-immunoprecipitation The EMBO journal High 10508164
2001 c-Myc transcriptionally represses the p27(Kip1) gene. The repression requires c-Myc homology box II, maps to a region -20 to +20 of the p27 promoter that contains a putative Inr element, and is facilitated by Max. c-Myc represses p27 promoter activity in multiple cell types including B cells, T cells, smooth muscle cells, and breast cancer cells. Promoter-luciferase reporter assays, co-transfection of c-Myc expression vectors, deletion/mutation analysis, Max co-transfection Oncogene Medium 11313917
1999 The Ah receptor (AhR) directly induces p27(Kip1) transcription without requiring ongoing protein synthesis or cell proliferation, and this induction mediates dioxin-induced suppression of cell proliferation. p27(Kip1) antisense-expressing cells are resistant to dioxin-mediated growth arrest, and thymuses from Kip1-deficient mice are largely resistant to dioxin-induced proliferation inhibition. Antisense expression, Kip1-knockout mouse tissue culture, transcription assays Genes & development High 10398686
2011 p27(Kip1) and p57(Kip2) cooperatively maintain hematopoietic stem cell (HSC) quiescence by retaining Hsc70/cyclin D1 complex in the cytoplasm. Combined deficiency of p57 and p27 in HSCs allows nuclear import of the Hsc70/cyclin D1 complex with concomitant Rb phosphorylation, causing severe defects in HSC quiescence and reduced transplantation capacity. Conditional double knockout mice, co-immunoprecipitation of Hsc70 with p57/p27, subcellular fractionation, transplantation assay Cell stem cell High 21885020
2001 Retinoblastoma protein (pRb) causes posttranscriptional accumulation of p27(KIP1) specifically bound to cyclin E, decreasing cyclin E-associated kinase activity, and this is required for pRb-mediated senescence. Ablation of p27(KIP1) expression by antisense reversibly abrogates pRb-induced cell cycle arrest and senescence. pRb reintroduction into RB(-/-) cells, western blot, kinase assays, antisense knockdown of p27 Molecular and cellular biology Medium 11340156
2004 Quaking (QKI) RNA binding proteins bind and stabilize p27(Kip1) mRNA, leading to increased p27(Kip1) protein accumulation in oligodendrocytes, thereby promoting cell cycle arrest and oligodendrocyte differentiation. QKI isoforms absent from Qk(v) mutant mice oligodendrocytes are required for this effect. RNA immunoprecipitation (mRNA binding assay), retroviral expression of QKI isoforms, mRNA stability assay, in vivo retroviral injection Nature neuroscience High 15568022
2006 Cytoplasmic p27(Kip1) promotes cell motility, survival, and tumorigenicity through modulation of Akt stability, independently of its cell cycle inhibitory function. A p27 mutant restricted to the cytoplasm (p27deltaNLS) downregulates RhoA and increases motility. RNA interference of cytoplasmic p27 in U87 glioma cells inhibits motility and survival and reduces Akt levels and tumorigenicity in vivo. Nuclear localization signal deletion mutant, RNAi knockdown, Akt turnover assays, xenograft tumor model Cancer research Medium 16489017
2005 p27(Kip1) and p21(Cip1) inhibit cell cycle progression and tumor suppression independently of CDK2; ectopic expression of p27(Kip1) efficiently inhibits cell cycle progression in Cdk2(-/-) fibroblasts, and loss of p27(Kip1) confers similar proliferative advantages regardless of Cdk2 status. Ablation of Cdk2 does not suppress phenotypic defects including pituitary tumors in p27(Kip1) null mice. Cdk2(-/-) mouse embryo fibroblasts, ectopic expression, double knockout mice, tumor analysis Cancer cell High 15950907
2012 p27(Kip1) controls cytokinesis through a CDK-independent mechanism by binding to and regulating citron kinase (citron-K), a Rho effector. p27 and citron-K colocalize at the contractile ring and mid-body during telophase and cytokinesis; p27 prevents citron-K interaction with its activator RhoA. A p27 mutant unable to bind or inhibit cyclin-CDK complexes (p27CK-) causes multinucleation and cytokinesis defects, rescued by expression of the minimal citron-K p27-binding domain. Co-immunoprecipitation, co-localization studies, rescue experiments with domain mutants, p27(CK-) knock-in mice The Journal of clinical investigation High 22293177
2012 p27 directly associates with the SRR2 enhancer of the Sox2 gene together with a p130-E2F4-SIN3A repressive complex to repress Sox2 transcription during differentiation. Sox2 haploinsufficiency genetically rescues gigantism, pituitary hyperplasia, pituitary tumors, and retinal defects characteristic of p27 null mice. ChIP assay, genetic epistasis (p27-null × Sox2 haploinsufficient mice), iPSC reprogramming without ectopic Sox2 Cell stem cell High 23217425
2015 Autophagy selectively degrades p27(Kip1) (CDKN1B) after TCR stimulation to allow T lymphocyte proliferation. p27(Kip1) forms polymers that associate physiologically with the autophagy receptor SQSTM1/p62. Genetic deletion of one allele of CDKN1B in autophagy-deficient T cells restores proliferative capability. Atg7-deficient T cells, adoptive transfer model, co-immunoprecipitation with SQSTM1/p62, genetic rescue by CDKN1B haploinsufficiency Autophagy High 26569626
2008 Protein kinase CK2-alpha' phosphorylates p27(Kip1) in response to angiotensin II (a cardiac growth factor), leading to proteasomal degradation of p27 in cardiomyocytes. Unphosphorylated p27 potently inhibits CK2-alpha', forming a regulatory feedback loop in differentiated cardiomyocytes that controls cardiac hypertrophic growth. In vitro kinase assay, co-immunoprecipitation, proteasome inhibitor experiments, CK2-alpha' knockdown/overexpression in cardiomyocytes Nature medicine High 18311148
2006 BRCA1 and FOXA1 cooperatively activate p27(Kip1) promoter transcription. FOXA1 binds a specific site within the BRCA1-responsive element of the p27(Kip1) promoter (-545 to -511), and co-expression of BRCA1 and FOXA1 synergistically activates the promoter. BRCA1 increases FOXA1 protein stability. BRCA1 siRNA reduces both FOXA1 expression and p27(Kip1) promoter activity. Promoter-luciferase reporter assay, EMSA with antibody supershift, siRNA knockdown, co-transfection, protein half-life assay Oncogene Medium 16331276
2005 MLL-AF4 fusion protein directly binds the CDKN1B (p27kip1) promoter and regulates its transcriptional activity in a cell-type-dependent manner (activating or repressing). Chromatin immunoprecipitation (ChIP) confirmed MLL-AF4 binding to the CDKN1B promoter in MLL-AF4 and MLL-AF9 leukemia cell lines. Chromatin immunoprecipitation (ChIP), luciferase reporter gene assay, inducible MLL-AF4 cell lines Proceedings of the National Academy of Sciences of the United States of America Medium 16169901
2012 p27(Kip1) integrates sequential phosphorylation signals from non-receptor tyrosine kinases (NRTKs) to regulate CDK4 activity and cell cycle entry. Abl phosphorylates p27 on Tyr88, facilitating a second modification on Tyr74 by Src; doubly tyrosine-phosphorylated p27 causes partial reactivation of Cdk4 within ternary complexes. Unmodified p27 inhibits Cdk4/cyclin D with IC50 ~1 nM. In vitro kinase assay, isothermal titration calorimetry, phosphorylation-specific analysis, Cdk4 activity reconstitution ACS chemical biology High 22276948
2017 Cytoplasmic p27(Kip1) promotes cell invasion by binding to Cortactin and facilitating its interaction with PAK1. p27 localizes to invadopodia and limits their number and stability. PAK1-mediated phosphorylation of Cortactin promotes invadopodia turnover, and expression of Cortactin mutants at PAK-targeted phosphorylation sites abolishes p27's effects on invadopodia dynamics. Co-immunoprecipitation, invadopodium formation assays, Cortactin phospho-mutants, PAK1 assays, p27 localization by fluorescence microscopy eLife High 28287395
2018 p27(Kip1) stabilizes α-tubulin acetyltransferase 1 (ATAT1), thereby promoting α-tubulin acetylation and proper axonal transport in cortical neurons. Suppression of the p27 ortholog dacapo in Drosophila disrupts axonal transport in vivo, causing locomotor defects. In vitro cortical neuron assays, Drosophila dacapo knockdown, ATAT1 stability assays, vesicle/organelle transport imaging Cell reports Medium 29791853
2016 PPM1G is a phosphatase that directly dephosphorylates p27(Kip1) at T198 in cells and in vitro. PPM1G interacts with p27, and its ectopic expression enhances p27 protein stability and delays G1-to-S cell cycle progression. PPM1G inhibits the interaction of p27 with 14-3-3θ, a chaperone that facilitates nuclear export. Knockdown of PPM1G accelerates p27 degradation and promotes cytoplasmic p27 localization. In vitro phosphatase assay, co-immunoprecipitation, knockdown/overexpression cell cycle analysis, subcellular fractionation American journal of cancer research Medium 27822412
2002 PGP9.5 (UCH-L1) interacts with JAB1 and forms a heteromeric complex containing p27(Kip1) in the nucleus of lung cancer cells. Under serum re-stimulation, nuclear translocation of both PGP9.5 and JAB1 coincides with reduced nuclear p27(Kip1) levels, suggesting PGP9.5 contributes to p27(Kip1) degradation via JAB1. Yeast two-hybrid, co-immunoprecipitation in vitro and in vivo, immunofluorescence co-localization Oncogene Medium 12082530
2006 Focal adhesion kinase (FAK) controls p27(Kip1) stability through Skp2-dependent mechanisms. Dominant-negative FAK (FRNK) impairs Skp2 mRNA expression, elevating p27 levels by reducing its degradation. Skp2-dependent degradation of p27 is required for endothelial cell proliferation and angiogenesis. Dominant-negative FAK expression, siRNA against Skp2 and p27, flow cytometry, DNA synthesis assay Molecular and cellular biology Medium 16705171
2009 AP-1 transcription factors (Jun/Fos heterodimers) mediate mitogen-induced transcriptional repression of the p27(Kip1) gene. An AP-1 element at position -469 in the human p27(Kip1) promoter is required for mitogen-induced down-regulation. Both MAPK and PI3K pathways mediate this transcriptional repression. Promoter-luciferase reporter assay, site-directed mutagenesis of AP-1 element, chromatin immunoprecipitation, enforced expression of Jun/Fos The Journal of biological chemistry Medium 19959471
2017 FLT3 and oncogenic FLT3-ITD directly bind and phosphorylate p27(Kip1) at tyrosine residue 88, inactivating its CDK-inhibitory function and promoting cell cycle progression in acute myeloid leukemia. FLT3 inhibition with AC220 reduces p27 Y88 phosphorylation and causes cell cycle arrest. Src family kinases also phosphorylate p27 Y88 in some FLT3-ITD-positive AML cells. Direct binding assay, in vitro phosphorylation, phospho-specific antibodies, FLT3 inhibitor treatment, primary patient samples Haematologica High 28522571
2013 p21(Cip1) and p27(Kip1) bind cyclin E, cyclin A, and CDK2 in postnatal cardiomyocytes and are required for cardiomyocyte cell cycle exit at G1 phase after birth. Knockout of p21 and p27 in mice results in failure of cardiomyocyte cell cycle exit at G1 and endoreplication. Co-immunoprecipitation of CDK complexes, p21/p27 knockout mice, flow cytometry of cardiomyocyte cell cycle distribution Biochemical and biophysical research communications Medium 24380855
2011 T198 modification of p27(Kip1) controls protein stability and cell motility through distinct mechanisms. The steric presence of threonine at position 198 (independent of phosphorylation) controls p27 stability via proteasome-dependent degradation through conformational changes in the disordered C-terminus, not through Skp2 binding. T198 phosphorylation specifically promotes p27/stathmin interaction and regulates cell motility. T198 point mutants, proteasome inhibitor assays, co-immunoprecipitation with Skp2 and stathmin, motility assays PloS one Medium 21423803
2016 CSN6 interacts with p27(Kip1) and facilitates ubiquitin-mediated proteasomal degradation of p27(Kip1) via COP1, an E3 ubiquitin ligase. COP1 overexpression causes cytoplasmic redistribution of p27, accelerating its degradation. CSN6-mediated p27 degradation depends on p27 nuclear export. Co-immunoprecipitation, siRNA knockdown, overexpression studies, subcellular fractionation, ubiquitination assay Cell cycle (Georgetown, Tex.) Medium 25945542
2014 Stathmin is a relevant p27(Kip1) binding partner in vivo, and genetic co-ablation of stathmin rescues most hyper-proliferative phenotypes of p27(Kip1) null mice (increased body/organ weight, retinal outgrowth, pituitary adenomas). The cooperativity of p27 and stathmin controls early G1-to-S phase transition, linked at the molecular level to decreased CDK4/6 kinase activity in double-knockout mice. Double-knockout mouse model, in vivo proliferation analysis, CDK kinase activity assays, gene expression profiling Cell cycle (Georgetown, Tex.) High 25486569
2019 BAP31 (B-cell receptor-associated protein 31) interacts with p27kip1 and promotes its proteasomal degradation. An intrabody (VH-D1) against BAP31 inhibits p27kip1 proteasome degradation by blocking the BAP31-p27kip1 interaction, resulting in reduced gastric cancer cell growth and tumor xenograft growth. Co-immunoprecipitation, intrabody expression, proteasome inhibitor assay, xenograft tumor model International journal of cancer Medium 30338855
2016 Nucleostemin (NS) promotes nucleolar polyubiquitylation of p27kip1, leading to p27 inactivation during hepatocellular carcinoma progression. p27 shows nucleolar distribution and interacts with NS; depletion of NS inhibits nucleolar polyubiquitylation of p27 and promotes p27 binding to CDK2-Cyclin E, inhibiting CDK2 activity and causing cell cycle arrest. Subcellular fractionation, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, CDK2 kinase assay Cancer letters Medium 27998760

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. The EMBO journal 682 17627278
1999 p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development (Cambridge, England) 454 10079221
1999 Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti. Proceedings of the National Academy of Sciences of the United States of America 299 10097167
1999 p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Genes & development 295 10398686
1999 Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1). The EMBO journal 277 10508164
2000 Multiple functions of p27(Kip1) and its alterations in tumor cells: a review. Journal of cellular physiology 251 10699962
2004 P27(kip1) down-regulation is associated with trastuzumab resistance in breast cancer cells. Cancer research 247 15173011
2001 p27(Kip1): regulation and function of a haploinsufficient tumor suppressor and its misregulation in cancer. Experimental cell research 247 11237531
2002 A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. The EMBO journal 241 12093740
2011 p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70. Cell stem cell 230 21885020
2001 Repression of transcription of the p27(Kip1) cyclin-dependent kinase inhibitor gene by c-Myc. Oncogene 227 11313917
2007 Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. The Journal of clinical endocrinology and metabolism 192 17519308
2010 Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors. Cell cycle (Georgetown, Tex.) 191 20519948
2005 Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1). Cancer cell 174 15950907
1996 p27/Kip1 mutation found in breast cancer. Cancer research 169 8625318
2001 Role for p27(Kip1) in Vascular Smooth Muscle Cell Migration. Circulation 164 11413088
2001 ErbB2/neu kinase modulates cellular p27(Kip1) and cyclin D1 through multiple signaling pathways. Cancer research 163 11522658
2004 Protection of p27(Kip1) mRNA by quaking RNA binding proteins promotes oligodendrocyte differentiation. Nature neuroscience 145 15568022
2000 p27(Kip1) regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina. Developmental biology 144 10694424
2001 Requirement for p27(KIP1) in retinoblastoma protein-mediated senescence. Molecular and cellular biology 134 11340156
2000 Differential regulation of p27(Kip1) expression by mitogenic and hypertrophic factors: Involvement of transcriptional and posttranscriptional mechanisms. The Journal of cell biology 121 10662779
2012 p27(Kip1) directly represses Sox2 during embryonic stem cell differentiation. Cell stem cell 118 23217425
2008 Post-translational regulation of the tumor suppressor p27(KIP1). Cellular and molecular life sciences : CMLS 117 18636226
2006 Reduction of cytosolic p27(Kip1) inhibits cancer cell motility, survival, and tumorigenicity. Cancer research 112 16489017
2002 Understanding p27(kip1) deregulation in cancer: down-regulation or mislocalization. Cell cycle (Georgetown, Tex.) 109 12548012
2012 MiR-196a is upregulated in gastric cancer and promotes cell proliferation by downregulating p27(kip1). Molecular cancer therapeutics 108 22343731
1999 Neurotransmitter receptor activation triggers p27(Kip1 )and p21(CIP1) accumulation and G1 cell cycle arrest in oligodendrocyte progenitors. Development (Cambridge, England) 101 9927607
2013 miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27(kip1). Oncogene 94 23584484
2001 p21(Cip1) and p27(Kip1) regulate cell cycle reentry after hypoxic stress but are not necessary for hypoxia-induced arrest. Molecular and cellular biology 94 11158306
2000 Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 94 11118465
2002 Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1). Oncogene 93 12082530
1998 Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours. Oncogene 93 9467944
1999 Expression of p21(Cip1/Waf1/Sdi1) and p27(Kip1) cyclin-dependent kinase inhibitors during human hematopoiesis. Blood 91 10361114
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2008 Protein kinase CK2 links extracellular growth factor signaling with the control of p27(Kip1) stability in the heart. Nature medicine 84 18311148
2015 p27(Kip1) signaling: Transcriptional and post-translational regulation. The international journal of biochemistry & cell biology 83 26279144
2015 Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1. Autophagy 82 26569626
2013 CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell cycle exit of mammalian cardiomyocytes. Biochemical and biophysical research communications 82 24380855
2011 Somatic mutation and germline sequence abnormalities in CDKN1B, encoding p27Kip1, in sporadic parathyroid adenomas. The Journal of clinical endocrinology and metabolism 82 21289244
2002 Loss of p27(Kip1) but not p21(Cip1) decreases survival and synergizes with MYC in murine lymphomagenesis. The EMBO journal 78 12110586
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2013 PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.). PloS one 73 24098663
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2001 Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells. The Biochemical journal 67 11415463
2006 Focal adhesion kinase controls cellular levels of p27/Kip1 and p21/Cip1 through Skp2-dependent and -independent mechanisms. Molecular and cellular biology 66 16705171
2006 BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27(Kip1). Oncogene 65 16331276
2006 Loss of nuclear p27 (CDKN1B/KIP1) in colorectal cancer is correlated with microsatellite instability and CIMP. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 56 17086168
2005 The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression. Proceedings of the National Academy of Sciences of the United States of America 56 16169901
1999 The concurrent expression of p27(kip1) and cyclin D1 in epithelial ovarian tumors. Gynecologic oncology 56 10329035
2006 p27(Kip1) and cyclin E expression and breast cancer survival after treatment with adjuvant chemotherapy. Journal of the National Cancer Institute 55 17148774
2001 p27(Kip1) is important in modulating pulmonary artery smooth muscle cell proliferation. American journal of respiratory cell and molecular biology 54 11713109
2001 Role of p27(Kip1) in cAMP- and TGF-beta2-mediated antiproliferation in rabbit corneal endothelial cells. Investigative ophthalmology & visual science 51 11726615
2005 Methylation of tumor suppressor genes p16(INK4a), p27(Kip1) and E-cadherin in carcinogenesis. Oral oncology 50 15978859
2012 p27(Kip1) controls cytokinesis via the regulation of citron kinase activation. The Journal of clinical investigation 49 22293177
2001 Aberrant expression of p21(WAF1/CIP1) and p27(KIP1) in cervical carcinoma. Cancer letters 48 11595134
2006 TIMP-1 regulation of cell cycle in human breast epithelial cells via stabilization of p27(KIP1) protein. Oncogene 47 16407831
2004 Downregulation of Skp2 and p27/Kip1 synergistically induces apoptosis in T98G glioblastoma cells. Journal of molecular medicine (Berlin, Germany) 47 15605273
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2000 Induction of G(1) cell cycle arrest and p27(KIP1) increase by panaxydol isolated from Panax ginseng. Biochemical pharmacology 39 10704940
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2001 Expression and subcellular localization of the cyclin-dependent kinase inhibitor p27(Kip1) in epithelial ovarian cancer. Gynecologic oncology 20 11606087
2017 Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex. Neural development 19 28506232
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