Cyclin-dependent kinase inhibitor 1C

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Cyclin-dependent kinase inhibitor 1C (p57, Kip2)
Symbols CDKN1C ; BWCR; BWS; KIP2; WBS; p57; p57Kip2
External IDs OMIM600856 MGI104564 HomoloGene133549 GeneCards: CDKN1C Gene
RNA expression pattern
PBB GE CDKN1C 213348 at tn.png
PBB GE CDKN1C 213182 x at tn.png
PBB GE CDKN1C 216894 x at tn.png
More reference expression data
Species Human Mouse
Entrez 1028 12577
Ensembl ENSG00000129757 ENSMUSG00000037664
UniProt P49918 P49919
RefSeq (mRNA) NM_000076 NM_001161624
RefSeq (protein) NP_000067 NP_001155096
Location (UCSC) Chr 11:
2.88 – 2.89 Mb
Chr 7:
143.46 – 143.46 Mb
PubMed search [1] [2]

Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is protein which in humans is encoded by the CDKN1C imprinted gene.[1]


Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations of CDKN1C are implicated in sporadic cancers and Beckwith-Wiedemann syndrome suggesting that it is a tumor suppressor candidate.[1]

CDKN1C is a tumor suppressor human gene on chromosome 11 (11p15) and belongs to the cip/kip gene family. It encodes a cell cycle inhibitor that binds to G1 cyclin-CDK complexes.[2] Thus p57KIP2 causes arrest of the cell cycle in G1 phase.

Clinical significance[edit]

A mutation of this gene may lead to loss of control over the cell cycle leading to uncontrolled cellular proliferation. p57KIP2 has been associated with Beckwith-Wiedemann syndrome (BWS) which is characterized by increased risk of tumor formation in childhood.[3] Loss-of-function mutations in this gene have also been shown associated to the IMAGe syndrome (Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital anomalies).[4]


Cyclin-dependent kinase inhibitor 1C has been shown to interact with:


  1. ^ a b "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)". 
  2. ^ Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ (Mar 1995). "p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene". Genes & Development 9 (6): 650–62. doi:10.1101/gad.9.6.650. PMID 7729684. 
  3. ^ Hatada I, Nabetani A, Morisaki H, Xin Z, Ohishi S, Tonoki H, Niikawa N, Inoue M, Komoto Y, Okada A, Steichen E, Ohashi H, Fukushima Y, Nakayama M, Mukai T (Oct 1997). "New p57KIP2 mutations in Beckwith-Wiedemann syndrome". Human Genetics 100 (5-6): 681–3. doi:10.1007/s004390050573. PMID 9341892. 
  4. ^ Riccio A, Cubellis MV (Jul 2012). "Gain of function in CDKN1C". Nature Genetics 44 (7): 737–8. doi:10.1038/ng.2336. PMID 22735584. 
  5. ^ Yokoo T, Toyoshima H, Miura M, Wang Y, Iida KT, Suzuki H, Sone H, Shimano H, Gotoda T, Nishimori S, Tanaka K, Yamada N (Dec 2003). "p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus". The Journal of Biological Chemistry 278 (52): 52919–23. doi:10.1074/jbc.M309334200. PMID 14530263. 
  6. ^ Joaquin M, Watson RJ (Nov 2003). "The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain". The Journal of Biological Chemistry 278 (45): 44255–64. doi:10.1074/jbc.M308953200. PMID 12947099. 
  7. ^ Reynaud EG, Leibovitch MP, Tintignac LA, Pelpel K, Guillier M, Leibovitch SA (Jun 2000). "Stabilization of MyoD by direct binding to p57(Kip2)". The Journal of Biological Chemistry 275 (25): 18767–76. doi:10.1074/jbc.M907412199. PMID 10764802. 
  8. ^ Watanabe H, Pan ZQ, Schreiber-Agus N, DePinho RA, Hurwitz J, Xiong Y (Feb 1998). "Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen". Proceedings of the National Academy of Sciences of the United States of America 95 (4): 1392–7. doi:10.1073/pnas.95.4.1392. PMC 19016. PMID 9465025. 

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