Cyclin-dependent kinase inhibitor 1C

Cyclin-dependent kinase inhibitor 1C (p57, Kip2)
Identifiers
Symbols CDKN1C ; BWCR; BWS; KIP2; WBS; p57; p57Kip2
External IDs OMIM: 600856 MGI: 104564 HomoloGene: 133549 GeneCards: CDKN1C Gene
RNA expression pattern
More reference expression data
Orthologs
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

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

Function

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

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] Loss of p57 function is also implicated in complete hydatidiform moles.[5]

Interactions

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

References

  1. 1 2 "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. LeGallo, Robin D.; Stelow, Edward B.; Ramirez, Nilsa C.; Atkins, Kristen A. (2008-05-01). "Diagnosis of hydatidiform moles using p57 immunohistochemistry and HER2 fluorescent in situ hybridization". American Journal of Clinical Pathology 129 (5): 749–755. doi:10.1309/7XRL378C22W7APBT. ISSN 0002-9173. PMID 18426735.
  6. 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.
  7. 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.
  8. 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.
  9. 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.

Further reading

External links

This article is issued from Wikipedia - version of the Monday, March 07, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.