Cyclin-dependent kinase inhibitor 1C
Ensembl |
| ||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt |
| ||||||||
| RefSeq (mRNA) |
| ||||||||
| RefSeq (protein) |
| ||||||||
| Location (UCSC) | Chr 11: 2.88 – 2.89 Mb | n/a | |||||||
| PubMed search | [2] | n/a | |||||||
| View/Edit Human | |||
Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C imprinted gene.[3]
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
CDKN1C is a
.CDKN1C was found to lead to cancer cell
Research Methods
Since it has been identified that mutation to this tumor suppressing gene can have dramatic effects in a newborn such as macroglossia there has been great research to determine the genetic significance. CDKN1C is prone to error during the process of gene imprinting. The process of gene imprinting is in concert with DNA methylation. This goes makes the gene become transcriptionally silent from the paternal side allowing the maternal gene to be active.[6] If this gene fails to be properly methylated, or obtains a mutation, there will be a lack of cell cycle suppression leading to the pediatric tumor growth.[7]
Research methods for this gene have involved different sequencing methods such as Sanger Sequencing. This sequencing method is a three step process that involves PCR, Gel Electrophoresis, and computer analysis to determine DNA sequences.[8] Sequencing can be helpful in identifying base pair mutations. A study done to assess the phenotypic effects that mutations to this gene will have taken genetic sequencing of a cohort of individuals known to be effected by a mutation on this gene. [9] In this study, they found 37 mutations associated with 38 different pedigrees. This went to prove that mutations to the CDKN1C on chromosome 11 would in fact have phenotypic effects on individuals. These effects are further discussed through the different clinical cases that can occur.
Clinical significance
A
Interactions
Cyclin-dependent kinase inhibitor 1C has been shown to
References
- ^ a b c ENSG00000129757 GRCh38: Ensembl release 89: ENSG00000273707, ENSG00000129757 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)".
- PMID 7729684.
- PMID 34272384.
- ^ Amacher S. "Epigenetics Impriting" (PDF). University of California Berkeley.
- S2CID 5450674.
- ^ "Sanger Sequencing Steps & Method". Merck KGaA. Darmstadt, Germany.
- S2CID 37398295.
- S2CID 21120202.
- S2CID 205345787.
- PMID 18426735.
- PMID 14530263.
- PMID 12947099.
- PMID 10764802.
- PMID 9465025.
Further reading
- Seizinger BR (Dec 1991). "Genes associated with tumor suppression and growth control in the human nervous system". Cancer and Metastasis Reviews. 10 (4): 281–7. S2CID 22809027.
- Lee MH, Reynisdóttir I, Massagué J (Mar 1995). "Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution". Genes & Development. 9 (6): 639–49. PMID 7729683.
- 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. PMID 7729684.
- Matsuoka S, Thompson JS, Edwards MC, Bartletta JM, Grundy P, Kalikin LM, Harper JW, Elledge SJ, Feinberg AP (Apr 1996). "Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15". Proceedings of the National Academy of Sciences of the United States of America. 93 (7): 3026–30. PMID 8610162.
- Reid LH, Crider-Miller SJ, West A, Lee MH, Massagué J, Weissman BE (Mar 1996). "Genomic organization of the human p57KIP2 gene and its analysis in the G401 Wilms' tumor assay". Cancer Research. 56 (6): 1214–8. PMID 8640800.
- Tokino T, Urano T, Furuhata T, Matsushima M, Miyatsu T, Sasaki S, Nakamura Y (May 1996). "Characterization of the human p57KIP2 gene: alternative splicing, insertion/deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis". Human Genetics. 97 (5): 625–31. S2CID 1833559.
- 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 (Oct 1996). "An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome". Nature Genetics. 14 (2): 171–3. S2CID 1765772.
- Furuhata T, Tokino T, Urano T, Nakamura Y (Nov 1996). "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, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E (Apr 1997). "New functional activities for the p21 family of CDK inhibitors". Genes & Development. 11 (7): 847–62. PMID 9106657.
- 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. PMID 9465025.
- Bhuiyan ZA, Yatsuki H, Sasaguri T, Joh K, Soejima H, Zhu X, Hatada I, Morisaki H, Morisaki T, Mukai T (Mar 1999). "Functional analysis of the p57KIP2 gene mutation in Beckwith-Wiedemann syndrome". Human Genetics. 104 (3): 205–10. S2CID 25081259.
- Lam WW, Hatada I, Ohishi S, Mukai T, Joyce JA, Cole TR, Donnai D, Reik W, Schofield PN, Maher ER (Jul 1999). "Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation". Journal of Medical Genetics. 36 (7): 518–23. PMID 10424811.
- 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. PMID 10764802.
- Fink JR, LeBien TW (Apr 2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Experimental Hematology. 29 (4): 490–8. PMID 11301189.
- Kido K, Doerks A, Lochelt M, Flügel RM (Apr 2002). "Identification and functional characterization of an intragenic DNA binding site for the spumaretroviral trans-activator in the human p57Kip2 gene". The Journal of Biological Chemistry. 277 (14): 12032–9. PMID 11815601.
- Balint E, Phillips AC, Kozlov S, Stewart CL, Vousden KH (Mar 2002). "Induction of p57(KIP2) expression by p73beta". Proceedings of the National Academy of Sciences of the United States of America. 99 (6): 3529–34. PMID 11891335.
- Ito Y, Yoshida H, Nakano K, Kobayashi K, Yokozawa T, Hirai K, Matsuzuka F, Matsuura N, Kuma K, Miyauchi A (Apr 2002). "Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues". International Journal of Molecular Medicine. 9 (4): 373–6. PMID 11891530.
- Kikuchi T, Toyota M, Itoh F, Suzuki H, Obata T, Yamamoto H, Kakiuchi H, Kusano M, Issa JP, Tokino T, Imai K (Apr 2002). "Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors". Oncogene. 21 (17): 2741–9. PMID 11965547.
- Li Y, Nagai H, Ohno T, Yuge M, Hatano S, Ito E, Mori N, Saito H, Kinoshita T (Oct 2002). "Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype". Blood. 100 (7): 2572–7. S2CID 13999973.
External links
- GeneReviews/NIH/NCBI/UW entry on Beckwith-Wiedemann Syndrome
- CDKN1C human gene location in the UCSC Genome Browser.
- CDKN1C human gene details in the UCSC Genome Browser.