Cyclin-dependent kinase inhibitor 1C

Cyclin-dependent kinase inhibitor 1C (p57, Kip2)
Identifiers
Symbols	CDKN1C; BWCR; BWS; KIP2; WBS; p57
External IDs	OMIM: 600856 MGI: 104564 HomoloGene: 58 GeneCards: CDKN1C Gene
Gene Ontology Molecular function • protein kinase inhibitor activity • cyclin-dependent protein kinase inhibitor activity • protein binding Cellular component • nucleus • nucleolus • cytoplasm Biological process • regulation of cyclin-dependent protein kinase activity • G1 phase of mitotic cell cycle • negative regulation of transcription from RNA polymerase II promoter • cell cycle • cell cycle arrest • negative regulation of cell proliferation • positive regulation of transforming growth factor beta receptor signaling pathway • negative regulation of kinase activity • negative regulation of phosphorylation • neuron maturation • negative regulation of transcription, DNA-dependent • positive regulation of transcription, DNA-dependent • negative regulation of epithelial cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1028	12577
Ensembl	ENSG00000129757	ENSMUSG00000037664
UniProt	P49918	Q791X1
RefSeq (mRNA)	NM_000076.2	NM_009876
RefSeq (protein)	NP_000067.1	NP_034006
Location (UCSC)	Chr 11: 2.9 – 2.91 Mb	Chr 7: 150.64 – 150.65 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

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]

Interactions

Cyclin-dependent kinase inhibitor 1C has been shown to interact with MyoD,^[4] MYBL2,^[5] PCNA^[6] and LIMK1.^[7]

References

1. ^ ^{a b} "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1028. 
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. ^ Reynaud, E G; Leibovitch M P, Tintignac L A, Pelpel K, Guillier M, Leibovitch S A (Jun. 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. 
5. ^ Joaquin, Manel; Watson Roger J (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". J. Biol. Chem. (United States) 278 (45): 44255–64. doi:10.1074/jbc.M308953200. ISSN 0021-9258. PMID 12947099. 
6. ^ Watanabe, H; Pan Z Q, Schreiber-Agus N, DePinho R A, Hurwitz J, Xiong Y (Feb. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19016. 
7. ^ 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 (Dec. 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

• Seizinger BR (1992). "Genes associated with tumor suppression and growth control in the human nervous system.". Cancer Metastasis Rev. 10 (4): 281–7. doi:10.1007/BF00554790. PMID 1786629. 
• Lee MH, Reynisdóttir I, Massagué J (1995). "Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution.". Genes Dev. 9 (6): 639–49. doi:10.1101/gad.9.6.639. PMID 7729683. 
• Matsuoka S, Edwards MC, Bai C, et al. (1995). "p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene.". Genes Dev. 9 (6): 650–62. doi:10.1101/gad.9.6.650. PMID 7729684. 
• Matsuoka S, Thompson JS, Edwards MC, et al. (1996). "Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15.". Proc. Natl. Acad. Sci. U.S.A. 93 (7): 3026–30. doi:10.1073/pnas.93.7.3026. PMC 39755. PMID 8610162. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=39755. 
• Reid LH, Crider-Miller SJ, West A, et al. (1996). "Genomic organization of the human p57KIP2 gene and its analysis in the G401 Wilms' tumor assay.". Cancer Res. 56 (6): 1214–8. PMID 8640800. 
• Tokino T, Urano T, Furuhata T, et al. (1996). "Characterization of the human p57KIP2 gene: alternative splicing, insertion/deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis.". Hum. Genet. 97 (5): 625–31. doi:10.1007/BF02281873. PMID 8655143. 
• Hatada I, Ohashi H, Fukushima Y, et al. (1996). "An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome.". Nat. Genet. 14 (2): 171–3. doi:10.1038/ng1096-171. PMID 8841187. 
• Furuhata T, Tokino T, Urano T, Nakamura Y (1997). "Isolation of a novel GPI-anchored gene specifically regulated by p53; correlation between its expression and anti-cancer drug sensitivity.". Oncogene 13 (9): 1965–70. PMID 8934543. 
• LaBaer J, Garrett MD, Stevenson LF, et al. (1997). "New functional activities for the p21 family of CDK inhibitors.". Genes Dev. 11 (7): 847–62. doi:10.1101/gad.11.7.847. PMID 9106657. 
• Watanabe H, Pan ZQ, Schreiber-Agus N, et al. (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. 95 (4): 1392–7. doi:10.1073/pnas.95.4.1392. PMC 19016. PMID 9465025. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19016. 
• Bhuiyan ZA, Yatsuki H, Sasaguri T, et al. (1999). "Functional analysis of the p57KIP2 gene mutation in Beckwith-Wiedemann syndrome.". Hum. Genet. 104 (3): 205–10. doi:10.1007/s004390050937. PMID 10323243. 
• Lam WW, Hatada I, Ohishi S, et al. (1999). "Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation.". J. Med. Genet. 36 (7): 518–23. doi:10.1136/jmg.36.7.518. PMC 1734395. PMID 10424811. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734395. 
• Reynaud EG, Leibovitch MP, Tintignac LA, et al. (2000). "Stabilization of MyoD by direct binding to p57(Kip2).". J. Biol. Chem. 275 (25): 18767–76. doi:10.1074/jbc.M907412199. PMID 10764802. 
• Fink JR, LeBien TW (2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors.". Exp. Hematol. 29 (4): 490–8. doi:10.1016/S0301-472X(01)00619-1. PMID 11301189. 
• Kido K, Doerks A, Lochelt M, Flügel RM (2002). "Identification and functional characterization of an intragenic DNA binding site for the spumaretroviral trans-activator in the human p57Kip2 gene.". J. Biol. Chem. 277 (14): 12032–9. doi:10.1074/jbc.M108747200. PMID 11815601. 
• Blint E, Phillips AC, Kozlov S, et al. (2002). "Induction of p57(KIP2) expression by p73beta.". Proc. Natl. Acad. Sci. U.S.A. 99 (6): 3529–34. doi:10.1073/pnas.062491899. PMC 122557. PMID 11891335. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122557. 
• Ito Y, Yoshida H, Nakano K, et al. (2002). "Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues.". Int. J. Mol. Med. 9 (4): 373–6. PMID 11891530. 
• Kikuchi T, Toyota M, Itoh F, et al. (2002). "Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors.". Oncogene 21 (17): 2741–9. doi:10.1038/sj.onc.1205376. PMID 11965547. 
• Li Y, Nagai H, Ohno T, et al. (2002). "Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype.". Blood 100 (7): 2572–7. doi:10.1182/blood-2001-11-0026. PMID 12239171. 

External Links

• GeneReviews/NIH/NCBI/UW entry on Beckwith-Wiedemann Syndrome