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Gene Review

CDKN1C  -  cyclin-dependent kinase inhibitor 1C (p57,...

Homo sapiens

Synonyms: BWCR, BWS, Cyclin-dependent kinase inhibitor 1C, Cyclin-dependent kinase inhibitor p57, KIP2, ...
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Disease relevance of CDKN1C


Psychiatry related information on CDKN1C

  • PURPOSE: WBS is an autosomal dominant disorder that includes features such as developmental delay, cardiovascular anomalies, mental retardation and characteristic facial appearance [6].
  • Monocular and binocular visual depth perception was tested in 33 patients with WBS [7].
  • Patients with Williams-Beuren Syndrome (WBS, also known as Williams Syndrome) show many problems in motor activities requiring visuo-motor integration, such as walking stairs [7].
  • A comparative analysis of eating and sleeping behaviours in 28 Prader-Willi- and 32 Williams-Beuren syndrome children by psychometric instruments confirms excessive food-seeking behaviours in PWS and selective food refusal in WBS as specific problems [8].

High impact information on CDKN1C


Chemical compound and disease context of CDKN1C


Biological context of CDKN1C


Anatomical context of CDKN1C


Associations of CDKN1C with chemical compounds


Physical interactions of CDKN1C

  • Here we demonstrate that p57 regulates actin dynamics by binding and translocating LIMK-1 from the cytoplasm into the nucleus, which in turn results in a reorganization of actin fiber [26].

Regulatory relationships of CDKN1C


Other interactions of CDKN1C

  • Thus, control of cell cycle and suppression of cell transformation by p57 require both CDK and PCNA inhibitory activity, and disruption of either or both functions may lead to uncontrolled cell growth [29].
  • We have also found two novel silencer sequences; one is located in KvDMR, a region that is thought to contain the promoter for the KCNQ1OT1 transcript, and another is in the CDKN1C gene [30].
  • Mutation analyses of the two genes in 62 type 2 diabetic patients resulted in the discovery of seven variants of CDKN1C and two variants of CDK4 [5].
  • OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown [31].
  • Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors [31].

Analytical, diagnostic and therapeutic context of CDKN1C


  1. An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype. Murrell, A., Heeson, S., Cooper, W.N., Douglas, E., Apostolidou, S., Moore, G.E., Maher, E.R., Reik, W. Hum. Mol. Genet. (2004) [Pubmed]
  2. The focal form of persistent hyperinsulinemic hypoglycemia of infancy: morphological and molecular studies show structural and functional differences with insulinoma. Sempoux, C., Guiot, Y., Dahan, K., Moulin, P., Stevens, M., Lambot, V., de Lonlay, P., Fournet, J.C., Junien, C., Jaubert, F., Nihoul-Fekete, C., Saudubray, J.M., Rahier, J. Diabetes (2003) [Pubmed]
  3. Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer. Soejima, H., Nakagawachi, T., Zhao, W., Higashimoto, K., Urano, T., Matsukura, S., Kitajima, Y., Takeuchi, M., Nakayama, M., Oshimura, M., Miyazaki, K., Joh, K., Mukai, T. Oncogene (2004) [Pubmed]
  4. Epigenetic down-regulation of CDKN1C/p57KIP2 in pancreatic ductal neoplasms identified by gene expression profiling. Sato, N., Matsubayashi, H., Abe, T., Fukushima, N., Goggins, M. Clin. Cancer Res. (2005) [Pubmed]
  5. Studies of variations of the cyclin-dependent kinase inhibitor 1C and the cyclin-dependent kinase 4 genes in relation to type 2 diabetes mellitus and related quantitative traits. Nielsen, E.M., Hansen, L., Stissing, T., Yanagisawa, K., Borch-Johnsen, K., Poulsen, P., Vaag, A., Hansen, T., Pedersen, O. J. Mol. Med. (2005) [Pubmed]
  6. Voiding dysfunction and the Williams-Beuren syndrome: a clinical and urodynamic investigation. Sammour, Z.M., Gomes, C.M., Duarte, R.J., Trigo-Rocha, F.E., Srougi, M. J. Urol. (2006) [Pubmed]
  7. Visual depth processing in Williams-Beuren syndrome. Van der Geest, J.N., Lagers-van Haselen, G.C., van Hagen, J.M., Brenner, E., Govaerts, L.C., de Coo, I.F., Frens, M.A. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2005) [Pubmed]
  8. Specific eating and sleeping problems in Prader-Willi and Williams-Beuren syndrome. Sarimski, K. Child: care, health and development. (1996) [Pubmed]
  9. Disruption of an imprinted gene cluster by a targeted chromosomal translocation in mice. Cleary, M.A., van Raamsdonk, C.D., Levorse, J., Zheng, B., Bradley, A., Tilghman, S.M. Nat. Genet. (2001) [Pubmed]
  10. Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements. Lee, M.P., Hu, R.J., Johnson, L.A., Feinberg, A.P. Nat. Genet. (1997) [Pubmed]
  11. An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome. Hatada, I., Ohashi, H., Fukushima, Y., Kaneko, Y., Inoue, M., Komoto, Y., Okada, A., Ohishi, S., Nabetani, A., Morisaki, H., Nakayama, M., Niikawa, N., Mukai, T. Nat. Genet. (1996) [Pubmed]
  12. Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Lee, M.H., Reynisdóttir, I., Massagué, J. Genes Dev. (1995) [Pubmed]
  13. Mechanism for inactivation of the KIP family cyclin-dependent kinase inhibitor genes in gastric cancer cells. Shin, J.Y., Kim, H.S., Park, J., Park, J.B., Lee, J.Y. Cancer Res. (2000) [Pubmed]
  14. Inducible expression of p57KIP2 inhibits glioma cell motility and invasion. Sakai, K., Peraud, A., Mainprize, T., Nakayama, J., Tsugu, A., Hongo, K., Kobayashi, S., Rutka, J.T. J. Neurooncol. (2004) [Pubmed]
  15. Expression of p57(KIP2) potently blocks the growth of human astrocytomas and induces cell senescence. Tsugu, A., Sakai, K., Dirks, P.B., Jung, S., Weksberg, R., Fei, Y.L., Mondal, S., Ivanchuk, S., Ackerley, C., Hamel, P.A., Rutka, J.T. Am. J. Pathol. (2000) [Pubmed]
  16. Increased IGF-II protein affects p57kip2 expression in vivo and in vitro: implications for Beckwith-Wiedemann syndrome. Grandjean, V., Smith, J., Schofield, P.N., Ferguson-Smith, A.C. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  17. Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. Diaz-Meyer, N., Day, C.D., Khatod, K., Maher, E.R., Cooper, W., Reik, W., Junien, C., Graham, G., Algar, E., Der Kaloustian, V.M., Higgins, M.J. J. Med. Genet. (2003) [Pubmed]
  18. p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Matsuoka, S., Edwards, M.C., Bai, C., Parker, S., Zhang, P., Baldini, A., Harper, J.W., Elledge, S.J. Genes Dev. (1995) [Pubmed]
  19. Cell-cycle mechanisms involved in podocyte proliferation in cellular lesion of focal segmental glomerulosclerosis. Wang, S., Kim, J.H., Moon, K.C., Hong, H.K., Lee, H.S. Am. J. Kidney Dis. (2004) [Pubmed]
  20. Analysis of CDKN1C in Beckwith Wiedemann syndrome. Algar, E., Brickell, S., Deeble, G., Amor, D., Smith, P. Hum. Mutat. (2000) [Pubmed]
  21. Contrasting roles of p57(KIP2) and p21(WAF1/CIP1/SDI1) in transplanted human and bovine adrenocortical cells. Thomas, M., Popnikolov, N.K., Scott, C., Smith, J.R., Hornsby, P.J. Exp. Cell Res. (2001) [Pubmed]
  22. Induction of p57 is required for cell survival when exposed to green tea polyphenols. Hsu, S., Yu, F.S., Lewis, J., Singh, B., Borke, J., Osaki, T., Athar, M., Schuster, G. Anticancer Res. (2002) [Pubmed]
  23. Multiple mechanisms downregulate CDKN1C in human bladder cancer. Hoffmann, M.J., Florl, A.R., Seifert, H.H., Schulz, W.A. Int. J. Cancer (2005) [Pubmed]
  24. Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15. Matsuoka, S., Thompson, J.S., Edwards, M.C., Bartletta, J.M., Grundy, P., Kalikin, L.M., Harper, J.W., Elledge, S.J., Feinberg, A.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  25. Chromosome 11p15.5 regional imprinting: comparative analysis of KIP2 and H19 in human tissues and Wilms' tumors. Chung, W.Y., Yuan, L., Feng, L., Hensle, T., Tycko, B. Hum. Mol. Genet. (1996) [Pubmed]
  26. p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus. Yokoo, T., Toyoshima, H., Miura, M., Wang, Y., Iida, K.T., Suzuki, H., Sone, H., Shimano, H., Gotoda, T., Nishimori, S., Tanaka, K., Yamada, N. J. Biol. Chem. (2003) [Pubmed]
  27. ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome. Arima, T., Kamikihara, T., Hayashida, T., Kato, K., Inoue, T., Shirayoshi, Y., Oshimura, M., Soejima, H., Mukai, T., Wake, N. Nucleic Acids Res. (2005) [Pubmed]
  28. p57(KIP2) is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57(KIP2), IGF2, and H19. Hartmann, W., Waha, A., Koch, A., Goodyer, C.G., Albrecht, S., von Schweinitz, D., Pietsch, T. Am. J. Pathol. (2000) [Pubmed]
  29. Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen. Watanabe, H., Pan, Z.Q., Schreiber-Agus, N., DePinho, R.A., Hurwitz, J., Xiong, Y. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  30. Insulator and silencer sequences in the imprinted region of human chromosome 11p15.5. Du, M., Beatty, L.G., Zhou, W., Lew, J., Schoenherr, C., Weksberg, R., Sadowski, P.D. Hum. Mol. Genet. (2003) [Pubmed]
  31. Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors. Barzon, L., Chilosi, M., Fallo, F., Martignoni, G., Montagna, L., Palù, G., Boscaro, M. Eur. J. Endocrinol. (2001) [Pubmed]
  32. Transforming growth factor beta-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation. Scandura, J.M., Boccuni, P., Massagué, J., Nimer, S.D. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  33. Alternative mechanisms associated with silencing of CDKN1C in Beckwith-Wiedemann syndrome. Diaz-Meyer, N., Yang, Y., Sait, S.N., Maher, E.R., Higgins, M.J. J. Med. Genet. (2005) [Pubmed]
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