cyclin dependent kinase inhibitor p57


Summary: A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.

Top Publications

  1. Liu W, Liu J, Ao L, Zhou Z, Zhou Y, Cui Z, et al. Epigenetic silencing of cell cycle regulatory genes during 3-methylcholanthrene and diethylnitrosamine-induced multistep rat lung cancer. Mol Carcinog. 2010;49:556-65 pubmed publisher
  2. Kanazawa T, Kommareddi P, Iwashita T, Kumar B, Misawa K, Misawa Y, et al. Galanin receptor subtype 2 suppresses cell proliferation and induces apoptosis in p53 mutant head and neck cancer cells. Clin Cancer Res. 2009;15:2222-30 pubmed publisher
    ..These were not observed with GALR1. This study shows that GALR2 reexpression can inhibit cell proliferation and induce apoptosis in HNSCC cells with mutant p53. GALR2 may be a feasible target for HNSCC therapy. ..
  3. Saravanamuthu S, Gao C, Zelenka P. Notch signaling is required for lateral induction of Jagged1 during FGF-induced lens fiber differentiation. Dev Biol. 2009;332:166-76 pubmed publisher
    ..These results demonstrate that Notch-mediated lateral induction of Jag1 is an essential component of FGF-dependent lens fiber cell differentiation. ..
  4. Laine H, Sulg M, Kirjavainen A, Pirvola U. Cell cycle regulation in the inner ear sensory epithelia: role of cyclin D1 and cyclin-dependent kinase inhibitors. Dev Biol. 2010;337:134-46 pubmed publisher
    ..Thus, cyclin D1 critically contributes to the proliferative plasticity of supporting cells. These data suggest that targeted cyclin D1 induction in supporting cells might be an avenue for proliferative regeneration in the inner ear. ..
  5. Ky N, Lim C, Li J, Tam J, Hamza M, Zhao Y. KLF4 suppresses HDACi induced caspase activation and the SAPK pathway by targeting p57(Kip2). Apoptosis. 2009;14:1095-107 pubmed publisher
    ..Results of our study demonstrate an unexpected antiapoptotic function of KLF4, and suggest an important cell fate determinant following histone deacetylase inhibitor induced apoptosis. ..
  6. Murphy K, McConnell T, Hafez M, Vang R, Ronnett B. Molecular genotyping of hydatidiform moles: analytic validation of a multiplex short tandem repeat assay. J Mol Diagn. 2009;11:598-605 pubmed publisher
    ..To avoid these pitfalls, we have developed an algorithm with quantitative guidelines for the interpretation of short tandem repeat genotyping data. ..
  7. Croucher D, Rickwood D, Tactacan C, Musgrove E, Daly R. 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. Mol Cell Biol. 2010;30:5057-70 pubmed publisher
  8. Drouin J, Bilodeau S, Roussel Gervais A. Stem cells, differentiation and cell cycle control in pituitary. Front Horm Res. 2010;38:15-24 pubmed publisher
    ..While these data revealed a new transient intermediate between progenitors and differentiated cells, they also raised new questions and suggested that separate signals may control differentiation and cell cycle. ..
  9. Romanelli V, Belinchón A, Benito Sanz S, Martinez Glez V, Gracia Bouthelier R, Heath K, et al. CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: Genotype-phenotype correlations, novel mutations, and polymorphisms. Am J Med Genet A. 2010;152A:1390-7 pubmed publisher
    ..The clinical observation of these malformations may help to decide which genetic characterization should be undertaken (i.e., CDKN1C screening), thus optimizing the laboratory evaluation for BWS. ..

More Information


  1. Ma Y, Chen L, Wright G, Pillai S, Chellappan S, Cress W. CDKN1C negatively regulates RNA polymerase II C-terminal domain phosphorylation in an E2F1-dependent manner. J Biol Chem. 2010;285:9813-22 pubmed publisher
    ..A central E2F1 domain interacts directly with CDKN1C, whereas a C-terminal E2F1 domain interacts with CDKN1C via interaction with Rb. The results presented in this report highlight a novel mechanism of tumor suppression by CDKN1C. ..
  2. Han L, SZABO P, Mann J. Postnatal survival of mice with maternal duplication of distal chromosome 7 induced by a Igf2/H19 imprinting control region lacking insulator function. PLoS Genet. 2010;6:e1000803 pubmed publisher
    ..Our results are consistent with the idea that reduced expression of IGF2 plays a role in the aetiology of the human imprinting-related growth-deficit disorder, Silver-Russell syndrome. ..
  3. Jin M, Zhang X, Hung P, Zhang S, Zhang L, Tang P. [Analysis on the relationship between p57 and cholesterol in cellular membrane]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010;26:25-7 pubmed
    ..No relationship between p57 and cholesterol in cellular membrane was found in the physiological condition, which is obviously different from that in pathological condition caused by the invasion of pathogenic mycobacteria. ..
  4. Akaishi K, Nakayama J, Sakai K, Kobayashi T, Rutka J. Antigen p57/Kip2 as a potential negative regulator of human astrocytoma growth. J Clin Neurosci. 2009;16:1615-8 pubmed publisher
    ..These findings suggest that p57/Kip2 inhibits the growth of human astrocytomas, and may function in parallel with p16 and p53. However, p57/Kip2 is, by itself, insufficient to arrest the cellular proliferation of human astrocytomas. ..
  5. Solomon L, Li J, Berube N, Beier F. Loss of ATRX in chondrocytes has minimal effects on skeletal development. PLoS ONE. 2009;4:e7106 pubmed publisher
    ..These findings indicate that ATRX is not directly required for development or growth of cartilage in the mouse, suggesting that the short stature in ATR-X patients is caused by defects in cartilage-extrinsic mechanisms. ..
  6. Lang B, Zhao L, Cai L, McKie L, Forrester J, McCaig C, et al. GABAergic amacrine cells and visual function are reduced in PAC1 transgenic mice. Neuropharmacology. 2010;58:215-25 pubmed publisher
    ..These data demonstrate that an appropriate level of PACAP signaling is required for normal retinogenesis and visual function. This finding may have implications in GABAergic neuron-related neurological conditions. ..
  7. Mitra P, Ghule P, van der Deen M, Medina R, Xie R, Holmes W, et al. CDK inhibitors selectively diminish cell cycle controlled activation of the histone H4 gene promoter by p220NPAT and HiNF-P. J Cell Physiol. 2009;219:438-48 pubmed publisher
    ..We conclude that CKIs selectively control stimulation of the histone H4 gene promoter by the p220(NPAT)/HiNF-P complex. ..
  8. Susaki E, Nakayama K, Yamasaki L, Nakayama K. Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model. Proc Natl Acad Sci U S A. 2009;106:5192-7 pubmed publisher
    ..Thus, these observations indicate that p57 and p27 share many characteristics in vivo, but that p57 also performs specific functions not amenable to substitution with p27. ..
  9. Sinuani I, Weissgarten J, Beberashvili I, Rapoport M, Sandbank J, Feldman L, et al. The cyclin kinase inhibitor p57kip2 regulates TGF-beta-induced compensatory tubular hypertrophy: effect of the immunomodulator AS101. Nephrol Dial Transplant. 2009;24:2328-38 pubmed publisher
    ..These results demonstrate that TGF-beta-induced compensatory tubular cell hypertrophy is regulated in vivo by p57(kip2) but not by the p21(Waf1) and p27(kip1) cyclin kinase inhibitor proteins. ..
  10. Romanelli V, Belinchon A, Campos Barros A, Heath K, Garcia Minaur S, Martinez Glez V, et al. CDKN1C mutations in HELLP/preeclamptic mothers of Beckwith-Wiedemann Syndrome (BWS) patients. Placenta. 2009;30:551-4 pubmed publisher
    ..To the best of our knowledge this is the first report of CDKN1C mutations in children born to women with preeclampsia/HELLP syndrome, thus suggesting the involvement of an imprinted gene in the pathophysiology of preeclampsia. ..
  11. McConnell T, Murphy K, Hafez M, Vang R, Ronnett B. Diagnosis and subclassification of hydatidiform moles using p57 immunohistochemistry and molecular genotyping: validation and prospective analysis in routine and consultation practice settings with development of an algorithmic approach. Am J Surg Pathol. 2009;33:805-17 pubmed publisher
  12. Madhavan J, Mallikarjuna K, Vikas K, George R, Bremner R, Kumaramanickavel G. CDKN1C (p57KIP2) mRNA expression in human retinoblastomas. Ophthalmic Genet. 2010;31:141-6 pubmed publisher
    ..Quantify cyclin dependent kinase inhibitor 1C (CDKN1C or p57KIP2) mRNA levels in human retinoblastoma tumors (RB) and associate with disease phenotype...
  13. Guo H, Tian T, Nan K, Wang W. p57: A multifunctional protein in cancer (Review). Int J Oncol. 2010;36:1321-9 pubmed
  14. Yang X, Karuturi R, Sun F, Aau M, Yu K, Shao R, et al. CDKN1C (p57) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells. PLoS ONE. 2009;4:e5011 pubmed publisher
    ..Importantly, as a newly identified EZH2 target with prognostic value, it has implications in patient stratification for cancer therapeutic targeting EZH2-mediated gene repression. ..
  15. Kipp B, Ketterling R, Oberg T, Cousin M, Plagge A, Wiktor A, et al. Comparison of fluorescence in situ hybridization, p57 immunostaining, flow cytometry, and digital image analysis for diagnosing molar and nonmolar products of conception. Am J Clin Pathol. 2010;133:196-204 pubmed publisher
    ..These data suggest that the combination of p57 and FISH seems to be the best ancillary testing strategy to aid pathologists in the appropriate identification of CM, PM, and HA in POC specimens. ..
  16. Kremer D, Heinen A, Jadasz J, Göttle P, Zimmermann K, Zickler P, et al. p57kip2 is dynamically regulated in experimental autoimmune encephalomyelitis and interferes with oligodendroglial maturation. Proc Natl Acad Sci U S A. 2009;106:9087-92 pubmed publisher
    ..These data suggest that sustained down-regulation of p57kip2 is important for oligodendroglial maturation and open perspectives for future therapeutic approaches to overcome the endogenous remyelination blockade in multiple sclerosis. ..
  17. Masuda K, Ishikawa Y, Onoyama I, Unno M, de Alboran I, Nakayama K, et al. Complex regulation of cell-cycle inhibitors by Fbxw7 in mouse embryonic fibroblasts. Oncogene. 2010;29:1798-809 pubmed publisher
    ..In contrast, the upregulation of p16(Ink4a) appeared to be independent of c-Myc. These results indicate that cell-cycle inhibitors undergo complex regulation by the Fbxw7-mediated proteolytic system. ..
  18. Monahan P, Rybak S, Raetzman L. The notch target gene HES1 regulates cell cycle inhibitor expression in the developing pituitary. Endocrinology. 2009;150:4386-94 pubmed publisher
  19. McConnell T, Norris Kirby A, Hagenkord J, Ronnett B, Murphy K. Complete hydatidiform mole with retained maternal chromosomes 6 and 11. Am J Surg Pathol. 2009;33:1409-15 pubmed publisher
    ..Genome-wide analysis has the potential to assist in localizing imprinted genes critical for determining the morphologic and behavioral phenotypes of hydatidiform moles. ..
  20. Sengupta S, Nie J, Wagner R, Yang C, Stewart R, Thomson J. MicroRNA 92b controls the G1/S checkpoint gene p57 in human embryonic stem cells. Stem Cells. 2009;27:1524-8 pubmed publisher
    ..Thus, we show that the miRNA miR-92b directly downregulates protein levels of the G(1)/S checkpoint gene p57. STEM CELLS 2009;27:1524-1528. ..
  21. Bliek J, Snijder S, Maas S, Polstra A, van der Lip K, Alders M, et al. Phenotypic discordance upon paternal or maternal transmission of duplications of the 11p15 imprinted regions. Eur J Med Genet. 2009;52:404-8 pubmed publisher
    ..However, no change in phenotype is observed if the duplication is transmitted through the mother suggesting that increased dosage of maternally expressed genes in the duplicated region has limited effect on the phenotype. ..
  22. Vlachos P, Joseph B. The Cdk inhibitor p57(Kip2) controls LIM-kinase 1 activity and regulates actin cytoskeleton dynamics. Oncogene. 2009;28:4175-88 pubmed publisher
  23. Joseph B, Andersson E, Vlachos P, Sodersten E, Liu L, Teixeira A, et al. p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural stem cells. Cell Death Differ. 2009;16:1256-65 pubmed publisher
    ..Our data suggest a novel role for p57Kip2 as a context-dependent repressor of neurogenic transcription factors and telencephalic neuronal differentiation. ..
  24. Susaki E, Nakayama K. Functional similarities and uniqueness of p27 and p57: insight from a knock-in mouse model. Cell Cycle. 2009;8:2497-501 pubmed
    ..Our findings also highlight and provide insight into the question of what determines the distinct cellular responses to abnormal cell cycling induced by the loss of CKIs. ..
  25. Kiselyuk A, Farber Katz S, Cohen T, Lee S, Geron I, Azimi B, et al. Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen. J Biomol Screen. 2010;15:663-70 pubmed publisher
  26. Hagiwara K, Li Y, Kinoshita T, Kunishma S, Ohashi H, Hotta T, et al. Aberrant DNA methylation of the p57KIP2 gene is a sensitive biomarker for detecting minimal residual disease in diffuse large B cell lymphoma. Leuk Res. 2010;34:50-4 pubmed publisher
    ..In this study, we established a convenient and universal method for detecting MRD in DLBCL. This technique is applicable for over 80% of patients with DLBCL. This could promote systemic MRD studies in the area of DLBCL. ..
  27. Boque N, Campion J, Milagro F, Moreno Aliaga M, Martinez J. Some cyclin-dependent kinase inhibitors-related genes are regulated by vitamin C in a model of diet-induced obesity. Biol Pharm Bull. 2009;32:1462-8 pubmed
    ..Thus, hepatic mRNA changes induced by ascorbic acid indicate a possible role of these genes in diet-induced oxidative stress processes. ..
  28. Wurz K, Garcia R, Goff B, Mitchell P, Lee J, Tewari M, et al. MiR-221 and MiR-222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survival. Genes Chromosomes Cancer. 2010;49:577-84 pubmed publisher
    ..01). In contrast, CDKN1B expression was not associated with miR-221 or miR-222 expression. Neither somatic mutations nor methylation of the studied region explained the alterations in miR-221 and miR-222 expression in most carcinomas. ..
  29. Lee S, Lee J, Jin S, Lee K, Sohn J, Chae S, et al. Expression of cell-cycle regulators (cyclin D1, cyclin E, p27kip1, p57kip2) in papillary thyroid carcinoma. Otolaryngol Head Neck Surg. 2010;142:332-7 pubmed publisher
    ..Our results suggest that immunohistochemistry of certain cell-cycle regulators may be helpful in the diagnosis of papillary thyroid carcinoma, and that cyclin D1 in particular may be a useful marker for evaluating lymph node metastasis. ..
  30. Romito A, Lonardo E, Roma G, Minchiotti G, Ballabio A, Cobellis G. Lack of sik1 in mouse embryonic stem cells impairs cardiomyogenesis by down-regulating the cyclin-dependent kinase inhibitor p57kip2. PLoS ONE. 2010;5:e9029 pubmed publisher
    ..Collectively, we provided evidence that sik1-mediated effects are specific for cardiomyogenesis regulating cardiomyoblast cell cycle exit toward terminal differentiation. ..
  31. Penaherrera M, Weindler S, Van Allen M, Yong S, Metzger D, McGillivray B, et al. Methylation profiling in individuals with Russell-Silver syndrome. Am J Med Genet A. 2010;152A:347-55 pubmed publisher
    ..While the association of hypomethylation of the H19/IGF2 ICR1 is clear, the continuous distribution of methylation values among the patients and controls complicates the establishment of clear cut-offs for clinical diagnosis. ..
  32. Ye W, Mairet Coello G, Pasoreck E, Dicicco Bloom E. Patterns of p57Kip2 expression in embryonic rat brain suggest roles in progenitor cell cycle exit and neuronal differentiation. Dev Neurobiol. 2009;69:1-21 pubmed publisher
  33. Rajaraman G, Murthi P, Pathirage N, Brennecke S, Kalionis B. Downstream targets of homeobox gene HLX show altered expression in human idiopathic fetal growth restriction. Am J Pathol. 2010;176:278-87 pubmed publisher
    ..We conclude that cell cycle regulatory genes RB1, MYC, CCNB1, ELK1, JUN, and CDKN1C, which control important trophoblast cell functions, are targets of HLX. ..
  34. Pateras I, Apostolopoulou K, Niforou K, Kotsinas A, Gorgoulis V. p57KIP2: "Kip"ing the cell under control. Mol Cancer Res. 2009;7:1902-19 pubmed publisher
  35. Qian K, Hu L, Chen H, Li H, Liu N, Li Y, et al. Hsa-miR-222 is involved in differentiation of endometrial stromal cells in vitro. Endocrinology. 2009;150:4734-43 pubmed publisher
  36. Van Rechem C, Boulay G, Pinte S, Stankovic Valentin N, Guerardel C, Leprince D. Differential regulation of HIC1 target genes by CtBP and NuRD, via an acetylation/SUMOylation switch, in quiescent versus proliferating cells. Mol Cell Biol. 2010;30:4045-59 pubmed publisher
    ..Our results decipher a mechanistic link between two competitive posttranslational modifications of HIC1 and corepressor recruitment to specific genes, leading to growth control. ..
  37. Ishikawa N, Harada Y, Tokuyasu Y, Nagasaki M, Maruyama R. Re-evaluation of the histological criteria for complete hydatidiform mole: Comparison with the immunohistochemical diagnosis using p57KIP2 and CD34. Biomed Res. 2009;30:141-7 pubmed
    ..This observation may be applicable in the pathological diagnosis of the molar diseases. ..
  38. Hoffner L, Parks W, Swerdlow S, Carson J, Surti U. Simultaneous detection of imprinted gene expression (p57(KIP2)) and molecular cytogenetics (FICTION) in the evaluation of molar pregnancies. J Reprod Med. 2010;55:219-28 pubmed
    ..The FICTION technique is a valuable ancillary tool for simultaneously evaluating the genotype and p57(KIP2) expression in unusual molar pregnancies. ..
  39. Kim R, Lieberman M, Lee R, Shin K, Mehrazarin S, Oh J, et al. Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-beta signaling. Exp Cell Res. 2010;316:2600-8 pubmed publisher
    ..Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inhibiting the TGF-beta signaling pathway in NHOK. ..