Cyclin-dependent kinase inhibitor 1C

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Cyclin-dependent kinase inhibitor 1C (p57, Kip2)
Identifiers
Symbols CDKN1C ; BWCR; BWS; KIP2; WBS; p57; p57Kip2
External IDs OMIM600856 MGI104564 HomoloGene58 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
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:
2.9 – 2.91 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]

Function[edit]

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]

Interactions[edit]

Cyclin-dependent kinase inhibitor 1C has been shown to interact with MyoD,[5] MYBL2,[6] PCNA[7] and LIMK1.[8]

References[edit]

  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 (March 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 (October 1997). "New p57KIP2 mutations in Beckwith-Wiedemann syndrome". Human Genetics 100 (5-6): 681–3. doi:10.1007/s004390050573. PMID 9341892. 
  4. ^ Riccio, Andrea; Cubellis, Maria Vittoria. "Gain of function in CDKN1C". Nature Genetics 44 (7): 737–738. doi:10.1038/ng.2336. 
  5. ^ Reynaud, E G; Leibovitch M P; Tintignac L A; Pelpel K; Guillier M; Leibovitch S A (June 2000). "Stabilization of MyoD by direct binding to p57(Kip2)". J. Biol. Chem. (UNITED STATES) 275 (25): 18767–76. doi:10.1074/jbc.M907412199. ISSN 0021-9258. PMID 10764802. 
  6. ^ Joaquin, Manel; Watson Roger J (November 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". J. Biol. Chem. (United States) 278 (45): 44255–64. doi:10.1074/jbc.M308953200. ISSN 0021-9258. PMID 12947099. 
  7. ^ Watanabe, H; Pan Z Q; Schreiber-Agus N; DePinho R A; Hurwitz J; Xiong Y (February 1998). "Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (4): 1392–7. doi:10.1073/pnas.95.4.1392. ISSN 0027-8424. PMC 19016. PMID 9465025. 
  8. ^ Yokoo, Tomotaka; Toyoshima Hideo, Miura Mitsuhiro, Wang Yuhui, Iida Kaoruko Tada, Suzuki Hiroaki, Sone Hirohito, Shimano Hitoshi, Gotoda Takanari, Nishimori Shigeki, Tanaka Keiji, Yamada Nobuhiro (December 2003). "p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus". J. Biol. Chem. (United States) 278 (52): 52919–23. doi:10.1074/jbc.M309334200. ISSN 0021-9258. PMID 14530263. 

Further reading[edit]

External links[edit]