Gene Symbol: Cdkn1c
Description: cyclin-dependent kinase inhibitor 1C (P57)
Alias: AL024410, CDKI, Kip2, p57(kip2), p57Kip2, cyclin-dependent kinase inhibitor 1C, cyclin-dependent kinase inhibitor p57
Species: mouse
Products:     Cdkn1c

Top Publications

  1. Korostowski L, Sedlak N, Engel N. The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart. PLoS Genet. 2012;8:e1002956 pubmed publisher
    ..Production of Kcnq1ot1 on the maternal chromosome does not silence Cdkn1c. We find that in later developmental stages, however, Kcnq1ot1 has a role in modulating Kcnq1 levels, since its ..
  2. 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. ..
  3. Umlauf D, Goto Y, Cao R, Cerqueira F, Wagschal A, Zhang Y, et al. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Nat Genet. 2004;36:1296-300 pubmed
  4. Onyango P, Miller W, Lehoczky J, Leung C, Birren B, Wheelan S, et al. Sequence and comparative analysis of the mouse 1-megabase region orthologous to the human 11p15 imprinted domain. Genome Res. 2000;10:1697-710 pubmed
    ..This study provides the first global view of the architecture of an entire imprinted domain and provides candidate sequence elements for subsequent functional analyses. ..
  5. Redrup L, Branco M, Perdeaux E, Krueger C, Lewis A, Santos F, et al. The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development. 2009;136:525-30 pubmed publisher
    ..Long ncRNAs in imprinting clusters and the Xist RNA on the inactive X chromosome thus appear to regulate epigenetic gene silencing by similar mechanisms. ..
  6. Shin J, Fitzpatrick G, Higgins M. Two distinct mechanisms of silencing by the KvDMR1 imprinting control region. EMBO J. 2008;27:168-78 pubmed the loss of imprinted expression of these genes in the placenta, it does not affect imprinted expression of Cdkn1c in a subset of embryonic tissues despite universal loss of paternal-specific methylation at Cdkn1c...
  7. Itoh Y, Masuyama N, Nakayama K, Nakayama K, Gotoh Y. The cyclin-dependent kinase inhibitors p57 and p27 regulate neuronal migration in the developing mouse neocortex. J Biol Chem. 2007;282:390-6 pubmed
    ..These results suggest that both p57 and p27 play essential roles in neuronal migration and may, in concert, coordinate the timing of neuronal differentiation, migration, and possibly cell cycle arrest in neocortical development. ..
  8. Wiley L, Dattilo L, Kang K, Giovannini M, Beebe D. The tumor suppressor merlin is required for cell cycle exit, terminal differentiation, and cell polarity in the developing murine lens. Invest Ophthalmol Vis Sci. 2010;51:3611-8 pubmed publisher
    ..The lens provides an assay system to identify pathways critical for fiber cell differentiation and to test therapies for the tumors that occur in patients with NF2. ..
  9. Hatada I, Nabetani A, Morisaki H, Xin Z, Ohishi S, Tonoki H, et al. New p57KIP2 mutations in Beckwith-Wiedemann syndrome. Hum Genet. 1997;100:681-3 pubmed
    ..Previously, we found p57KIP2, which is a Cdk-kinase inhibitor located at 11p15, is mutated in two BWS patients...

More Information


  1. Cerrato F, Sparago A, Di Matteo I, Zou X, Dean W, Sasaki H, et al. The two-domain hypothesis in Beckwith-Wiedemann syndrome: autonomous imprinting of the telomeric domain of the distal chromosome 7 cluster. Hum Mol Genet. 2005;14:503-11 pubmed
    ..However, the mechanisms by which imprinting of genes in the IC2 domain (e.g. Cdkn1c and Kcnq1) is regulated have not been well defined, and recent evidence indicates that distantly located cis-..
  2. Lee M, Reynisdottir I, Massague J. Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev. 1995;9:639-49 pubmed
    ..We have isolated a new member of the p21CIP1/p27KIP1 CDI family and named it p57KIP2 to denote its apparent molecular mass and higher similarity to p27KIP1...
  3. Tateishi Y, Matsumoto A, Kanie T, Hara E, Nakayama K, Nakayama K. Development of mice without Cip/Kip CDK inhibitors. Biochem Biophys Res Commun. 2012;427:285-92 pubmed publisher
  4. Dyer M, Cepko C. p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J Neurosci. 2001;21:4259-71 pubmed
    ..During the embryonic stages of development, when both p27(Kip1) and p57(Kip2) are expressed in retinal progenitor cells, they were found in distinct populations, demonstrating directly that ..
  5. Dyer M, Cepko C. p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina. Development. 2000;127:3593-605 pubmed
    ..We have found that the p57(Kip2) cyclin kinase inhibitor is upregulated during G(1)/G(0) in a subset of retinal progenitor cells exiting the cell ..
  6. Mancini Dinardo D, Steele S, Levorse J, Ingram R, Tilghman S. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev. 2006;20:1268-82 pubmed
    ..genes encoding the maternally expressed placental-specific transcription factor ASCL2, the cyclin-dependent kinase CDKN1C, and the potassium channel KCNQ1...
  7. Chen H, Shi S, Acosta L, Li W, Lu J, Bao S, et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development. 2004;131:2219-31 pubmed
    ..BMP10 null mice display ectopic and elevated expression of p57(kip2) and a dramatic reduction in proliferative activity in cardiomyocytes at E9.0-E9.5...
  8. Wigle J, Chowdhury K, Gruss P, Oliver G. Prox1 function is crucial for mouse lens-fibre elongation. Nat Genet. 1999;21:318-22 pubmed
    ..downregulated expression of the cell-cycle inhibitors Cdkn1b (also known as p27KIP1) and Cdkn1c (also known as p57KIP2), misexpression of E-cadherin and inappropriate apoptosis...
  9. Zhao H, Yang T, Madakashira B, Thiels C, Bechtle C, Garcia C, et al. Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation. Dev Biol. 2008;318:276-88 pubmed publisher
    ..proliferation in prospective lens fiber cells, reduced expression of the cell cycle inhibitors p27(kip1) and p57(kip2), increased apoptosis and aberrant or reduced expression of Prox1, Pax6, c-Maf, E-cadherin and alpha-, beta- and ..
  10. Riley P, Anson Cartwright L, Cross J. The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis. Nat Genet. 1998;18:271-5 pubmed
    ..Their heart tubes showed abnormal looping and ventricular myocardial differentiation. Therefore, Hand1 is essential for differentiation of both trophoblast and cardiomyocytes, which are embryologically distinct cell lineages. ..
  11. Gui H, Li S, Matise M. A cell-autonomous requirement for Cip/Kip cyclin-kinase inhibitors in regulating neuronal cell cycle exit but not differentiation in the developing spinal cord. Dev Biol. 2007;301:14-26 pubmed
    ..and post-mitotic neurons during early neurogenesis, with p27(Kip1) having the broadest expression, and both p57(Kip2) and p21(Cip1) showing transient expression in restricted populations...
  12. Tunster S, Van de Pette M, John R. Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome. Dis Model Mech. 2011;4:814-21 pubmed publisher
    Mutations in the imprinted CDKN1C gene are associated with the childhood developmental disorder Beckwith-Wiedemann syndrome (BWS)...
  13. Kanayama N, Takahashi K, Matsuura T, Sugimura M, Kobayashi T, Moniwa N, et al. Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice. Mol Hum Reprod. 2002;8:1129-35 pubmed
    b>p57Kip2, a potent inhibitor of several cyclin/cyclin dependent kinase complexes (CDK ), is a paternally imprinted gene in both humans and mice, and here we show that pregnant mice which are heterozygous for p57Kip2 deficiency display ..
  14. Tunster S, Tycko B, John R. The imprinted Phlda2 gene regulates extraembryonic energy stores. Mol Cell Biol. 2010;30:295-306 pubmed publisher
  15. Mohammad F, Mondal T, Guseva N, Pandey G, Kanduri C. Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development. 2010;137:2493-9 pubmed publisher
  16. Georgia S, Soliz R, Li M, Zhang P, Bhushan A. p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors. Dev Biol. 2006;298:22-31 pubmed
  17. Balint E, Phillips A, Kozlov S, Stewart C, Vousden K. Induction of p57(KIP2) expression by p73beta. Proc Natl Acad Sci U S A. 2002;99:3529-34 pubmed
    ..Our results suggest that p73 may regulate expression of genes through mechanisms that are not shared by p53, potentially explaining the different contributions of p53 and p73 to normal development. ..
  18. Zhang P, Wong C, Liu D, Finegold M, Harper J, Elledge S. p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step. Genes Dev. 1999;13:213-24 pubmed
    ..Here we show that two Cdk inhibitors, p21(CIP1) and p57(KIP2), redundantly control differentiation of skeletal muscle and alveoli in the lungs...
  19. Fitzpatrick G, Soloway P, Higgins M. Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet. 2002;32:426-31 pubmed that paternal inheritance of a deletion of KvDMR1 results in the de-repression in cis of six genes, including Cdkn1c, which encodes cyclin-dependent kinase inhibitor 1C...
  20. Matsumoto A, Takeishi S, Kanie T, Susaki E, Onoyama I, Tateishi Y, et al. p57 is required for quiescence and maintenance of adult hematopoietic stem cells. Cell Stem Cell. 2011;9:262-71 pubmed publisher
    ..Our results therefore suggest that, among Cip/Kip family CDK inhibitors, p57 plays a predominant role in the quiescence and maintenance of adult HSCs. ..
  21. Gould T, Pfeifer K. Imprinting of mouse Kvlqt1 is developmentally regulated. Hum Mol Genet. 1998;7:483-7 pubmed
    ..Late juvenile and adult animals show complete biallelism, suggesting an explanation for the lack of parent of origin bias in JLN and long QT. ..
  22. Lewis A, Mitsuya K, Umlauf D, Smith P, Dean W, Walter J, et al. Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation. Nat Genet. 2004;36:1291-5 pubmed
  23. Lovicu F, McAvoy J. Spatial and temporal expression of p57(KIP2) during murine lens development. Mech Dev. 1999;86:165-9 pubmed
    The expression patterns of p57(KIP2), an important cyclin-dependent kinase inhibitor in the lens, is investigated...
  24. Le T, Conley K, Mead T, Rowan S, Yutzey K, Brown N. Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development. Dev Dyn. 2012;241:493-504 pubmed publisher
    ..In addition, AP2?-Cre-mediated deletion of Rbpj resulted in embryos with cardiac outflow tract and liver deformities, and perinatal lethality. ..
  25. Chang T, Kim M, Ryoo K, Park J, Eom S, Shim J, et al. p57KIP2 modulates stress-activated signaling by inhibiting c-Jun NH2-terminal kinase/stress-activated protein Kinase. J Biol Chem. 2003;278:48092-8 pubmed
    b>p57KIP2, a member of the Cip/Kip family of enzymes that inhibit several cyclin-dependent kinases, plays a role in many biological events including cell proliferation, differentiation, apoptosis, tumorigenesis and developmental changes...
  26. Zhang P, Liegeois N, Wong C, Finegold M, Hou H, Thompson J, et al. Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature. 1997;387:151-8 pubmed
    Mice lacking the imprinted Cdk inhibitor p57(KIP2) have altered cell proliferation and differentiation, leading to abdominal muscle defects; cleft palate; endochondral bone ossification defects with incomplete differentiation of ..
  27. Engemann S, Strödicke M, Paulsen M, Franck O, Reinhardt R, Lane N, et al. Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprinting. Hum Mol Genet. 2000;9:2691-706 pubmed
    ..5. Here we focus on the adjacent sequences of 0.5 Mb including the KCNQ1/Kcnq1 and CDKN1C/Cdkn1c genes, which are implicated in BWS, and on one of the proposed boundary regions of the imprinting cluster...
  28. Kato R, Shirohzu H, Yokomine T, Mizuno S, Mukai T, Sasaki H. Sequence-ready 1-Mb YAC, BAC and cosmid contigs covering the distal imprinted region of mouse chromosome 7. DNA Res. 1999;6:401-5 pubmed
  29. Cain S, Martinez G, Kokkinos M, Turner K, Richardson R, Abud H, et al. Differential requirement for beta-catenin in epithelial and fiber cells during lens development. Dev Biol. 2008;321:420-33 pubmed publisher
    ..epithelial layer with loss of E-cadherin and Pax6 expression as well as abnormal expression of c-Maf and p57(kip2) but not Prox1...
  30. Caspary T, Cleary M, Perlman E, Zhang P, Elledge S, Tilghman S. Oppositely imprinted genes p57(Kip2) and igf2 interact in a mouse model for Beckwith-Wiedemann syndrome. Genes Dev. 1999;13:3115-24 pubmed
    ..5. A subset of BWS patients has been identified with loss-of-function mutations in p57(KIP2), a maternally expressed gene encoding a G(1) cyclin-dependent kinase inhibitor...
  31. Kerr C, Huang J, Williams T, West Mays J. Activation of the hedgehog signaling pathway in the developing lens stimulates ectopic FoxE3 expression and disruption in fiber cell differentiation. Invest Ophthalmol Vis Sci. 2012;53:3316-30 pubmed publisher
  32. Salas M, John R, Saxena A, Barton S, Frank D, Fitzpatrick G, et al. Placental growth retardation due to loss of imprinting of Phlda2. Mech Dev. 2004;121:1199-210 pubmed
    The maternally expressed/paternally silenced genes Phlda2 (a.k.a. Ipl/Tssc3), Slc22a1l, Cdkn1c, Kcnq1, and Ascl2 are clustered in an imprinted domain on mouse chromosome 7...
  33. Blixt A, Mahlapuu M, Aitola M, Pelto Huikko M, Enerback S, Carlsson P. A forkhead gene, FoxE3, is essential for lens epithelial proliferation and closure of the lens vesicle. Genes Dev. 2000;14:245-54 pubmed
    ..This implies that FoxE3 is essential for closure of the lens vesicle and is a factor that promotes survival and proliferation, while preventing differentiation, in the lens epithelium. ..
  34. John R, Ainscough J, Barton S, Surani M. Distant cis-elements regulate imprinted expression of the mouse p57( Kip2) (Cdkn1c) gene: implications for the human disorder, Beckwith--Wiedemann syndrome. Hum Mol Genet. 2001;10:1601-9 pubmed
    ..Only two of these genes, p57(KIP2) (CDKN1C) and IGF2, are likely to be functionally involved in this disease...
  35. Gabory A, Ripoche M, Le Digarcher A, Watrin F, Ziyyat A, Forné T, et al. H19 acts as a trans regulator of the imprinted gene network controlling growth in mice. Development. 2009;136:3413-21 pubmed publisher
    ..Our results also bring further experimental evidence for the existence of the IGN and open new perspectives in the comprehension of the role of genomic imprinting in embryonic growth and in human imprinting pathologies. ..
  36. Andrews S, Wood M, Tunster S, Barton S, Surani M, John R. Cdkn1c (p57Kip2) is the major regulator of embryonic growth within its imprinted domain on mouse distal chromosome 7. BMC Dev Biol. 2007;7:53 pubmed
    b>Cdkn1c encodes an embryonic cyclin-dependant kinase inhibitor that acts to negatively regulate cell proliferation and, in some tissues, to actively direct differentiation...
  37. Takahashi K, Kobayashi T, Kanayama N. p57(Kip2) regulates the proper development of labyrinthine and spongiotrophoblasts. Mol Hum Reprod. 2000;6:1019-25 pubmed
    The cyclin-dependent kinase (cdk) inhibitor, p57 (Kip2) is a tumour suppressor candidate and a paternally-imprinted gene. In humans, the p57(Kip2) gene is located on chromosome 11p15...
  38. Paulsen M, Davies K, Bowden L, Villar A, Franck O, Fuermann M, et al. Syntenic organization of the mouse distal chromosome 7 imprinting cluster and the Beckwith-Wiedemann syndrome region in chromosome 11p15.5. Hum Mol Genet. 1998;7:1149-59 pubmed
    ..We also localized Kcnq1 (Kvlqt1) and Cd81 (Tapa-1) between Cdkn1c (p57(Kip2)) and Mash2...
  39. Zhang P, Wong C, DePinho R, Harper J, Elledge S. Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development. Genes Dev. 1998;12:3162-7 pubmed
    ..In this study, using multiple mutant mice, we show that the Cdk inhibitors p27(KIP1) and p57(KIP2) function redundantly to control cell cycle exit and differentiation of lens fiber cells and placental trophoblasts...
  40. Joseph B, Wallén Mackenzie A, Benoit G, Murata T, Joodmardi E, Okret S, et al. p57(Kip2) cooperates with Nurr1 in developing dopamine cells. Proc Natl Acad Sci U S A. 2003;100:15619-24 pubmed
    ..Here we show that p57Kip2 is expressed in postmitotic differentiating midbrain dopamine cells...
  41. Westbury J, Watkins M, Ferguson Smith A, Smith J. Dynamic temporal and spatial regulation of the cdk inhibitor p57(kip2) during embryo morphogenesis. Mech Dev. 2001;109:83-9 pubmed
    The complete developmental expression pattern of the cyclin dependent kinase inhibitor (CDKI) p57(kip2) has not been reported, here we report a detailed study of the localization of p57(kip2) protein during mouse organogenesis...
  42. Borriello A, Caldarelli I, Bencivenga D, Criscuolo M, Cucciolla V, Tramontano A, et al. p57(Kip2) and cancer: time for a critical appraisal. Mol Cancer Res. 2011;9:1269-84 pubmed publisher
    ..molecular studies on animal models and patients with Beckwith-Wiedemann syndrome have shown that alterations in CDKN1C (the p57(Kip2) encoding gene) have functional relevance in the pathogenesis of this disease...
  43. Hatada I, Mukai T. Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse. Nat Genet. 1995;11:204-6 pubmed
    b>p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP is located on chromosome 11p15.5 (ref...
  44. Coan P, Conroy N, Burton G, Ferguson Smith A. Origin and characteristics of glycogen cells in the developing murine placenta. Dev Dyn. 2006;235:3280-94 pubmed
    ..Thus stereology and immunohistochemistry have provided useful insights into Jz development and function of the glycogen cells. ..
  45. MacLean H, Guo J, Knight M, Zhang P, Cobrinik D, Kronenberg H. The cyclin-dependent kinase inhibitor p57(Kip2) mediates proliferative actions of PTHrP in chondrocytes. J Clin Invest. 2004;113:1334-43 pubmed
    ..Because the bone phenotype of mice lacking the cyclin-dependent kinase inhibitor p57(Kip2) is the opposite of the PTHrP-null phenotype, we hypothesized that PTHrP's proliferative actions in chondrocytes ..
  46. Kochilas L, Li J, Jin F, Buck C, Epstein J. p57Kip2 expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium. Pediatr Res. 1999;45:635-42 pubmed
    ..One of the genes that we identified, p57Kip2, encodes a cyclin-dependent kinase inhibitor of the p21 family...
  47. Takahashi K, Nakayama K. Mice lacking a CDK inhibitor, p57Kip2, exhibit skeletal abnormalities and growth retardation. J Biochem. 2000;127:73-83 pubmed
    b>p57Kip2, one of the cyclin-dependent kinase (CDK) inhibitors, has been suggested to be a tumor suppressor candidate. To elucidate its biological roles in mouse development and tumorigenesis, we created p57Kip2-deficient mice...
  48. Matsuoka S, Edwards M, Bai C, Parker S, Zhang P, Baldini A, et al. p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev. 1995;9:650-62 pubmed
    ..We describe a new CKI, p57KIP2, which is related to p21CIP1 and p27KIP1...
  49. Yan Y, Frisen J, Lee M, Massague J, Barbacid M. Ablation of the CDK inhibitor p57Kip2 results in increased apoptosis and delayed differentiation during mouse development. Genes Dev. 1997;11:973-83 pubmed
    p57(Kip2) is a paternally imprinted gene that encodes a potent inhibitor of several cyclin/Cdk complexes...
  50. Caspary T, Cleary M, Baker C, Guan X, Tilghman S. Multiple mechanisms regulate imprinting of the mouse distal chromosome 7 gene cluster. Mol Cell Biol. 1998;18:3466-74 pubmed
    ..end of mouse chromosome 7 that contains a cluster of four maternally expressed genes, H19, Mash2, Kvlqt1, and p57(Kip2), as well as two paternally expressed genes, Igf2 and Ins2, and assess the expression and imprinting of Mash2, ..
  51. Zou P, Yoshihara H, Hosokawa K, Tai I, Shinmyozu K, Tsukahara F, et al. p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70. Cell Stem Cell. 2011;9:247-61 pubmed publisher
    ..Taken together, these data suggest that regulation of cytoplasmic localization of Hsc70/cyclin D1 complex by p57 and p27 is a key intracellular mechanism in controlling HSC dormancy. ..
  52. Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H, et al. Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation. Proc Natl Acad Sci U S A. 2003;100:10231-6 pubmed
    The abundance of the cyclin-dependent kinase (CDK) inhibitor p57Kip2, an important regulator of cell cycle progression, is thought to be controlled by the ubiquitin-proteasome pathway...
  53. John R, Hodges M, Little P, Barton S, Surani M. A human p57(KIP2) transgene is not activated by passage through the maternal mouse germline. Hum Mol Genet. 1999;8:2211-9 pubmed
    ..and the syntenic region on mouse distal chromosome 7, contain several imprinted genes, including p57 (KIP2) ( CDKN1C ) and IGF2...