CDKN1C

CDKN1C（cyclin-dependent kinase inhibitor 1C）またはp57^KIP2は、ヒトではCDKN1Cインプリンティング遺伝子によってコードされるタンパク質である^[5]。

CDKN1C
識別子
記号	CDKN1C, BWCR, BWS, KIP2, WBS, p57, p57Kip2, cyclin-dependent kinase inhibitor 1C, cyclin dependent kinase inhibitor 1C
外部ID	OMIM: 600856 MGI: 104564 HomoloGene: 133549 GeneCards: CDKN1C
遺伝子の位置 (ヒト) 染色体 11番染色体 (ヒト)[1] バンド データ無し 開始点 2,883,213 bp[1] 終点 2,885,775 bp[1]
遺伝子の位置 (マウス) 染色体 7番染色体 (マウス)[2] バンド データ無し 開始点 143,012,076 bp[2] 終点 143,014,787 bp[2]
RNA発現パターン さらなる参照発現データ
遺伝子オントロジー 分子機能 • 血漿タンパク結合 • cyclin-dependent protein serine/threonine kinase inhibitor activity • protein kinase inhibitor activity • protein-containing complex binding 細胞の構成要素 • 細胞質 • 細胞核 生物学的プロセス • positive regulation of transforming growth factor beta receptor signaling pathway • positive regulation of transcription, DNA-templated • regulation of mitotic cell cycle • negative regulation of epithelial cell proliferation • negative regulation of protein serine/threonine kinase activity • 細胞周期 • negative regulation of transcription, DNA-templated • negative regulation of kinase activity • negative regulation of cyclin-dependent protein kinase activity • negative regulation of phosphorylation • negative regulation of transcription by RNA polymerase II • 骨格系発生 • 腎臓発生 • 胎座 • regulation of exit from mitosis • 老化 • myeloid cell differentiation • 副腎発生 • multicellular organism growth • neuron maturation • camera-type eye development • negative regulation of cyclin-dependent protein serine/threonine kinase activity • 消化器系発生 • 子宮発生 • embryonic placenta morphogenesis • genetic imprinting • regulation of lens fiber cell differentiation 出典:Amigo / QuickGO
オルソログ
種	ヒト	マウス
Entrez	1028	12577
Ensembl	ENSG00000273707 ENSG00000129757	ENSMUSG00000037664
UniProt	P49918	P49919
RefSeq (mRNA)	NM_000076 NM_001122630 NM_001122631 NM_001362474 NM_001362475	NM_001161624 NM_009876 NM_001354981
RefSeq (タンパク質)	NP_000067 NP_001116102 NP_001116103 NP_001349403 NP_001349404	NP_001155096 NP_034006 NP_001341910
場所 (UCSC)	Chr 11: 2.88 – 2.89 Mb	Chr 11: 143.01 – 143.01 Mb
PubMed検索	[3]	[4]
ウィキデータ
閲覧/編集 ヒト 閲覧/編集 マウス

機能

CDKN1C遺伝子はヒトの11番染色体（英語版）（11p15）に位置し、cip/kip遺伝子ファミリーに属する^[6]。CDKN1CはいくつかのG₁期サイクリン/CDK複合体に強固に結合する阻害因子、そして細胞増殖の負の調節因子である^[5][6]。CDKN1Cの変異は散発性がんやベックウィズ・ヴィーデマン症候群（英語版）への関与が示唆されており、CDKN1Cががん抑制因子であることが示唆される^[5]。

臨床的意義

CDKN1C遺伝子の変異は細胞周期の制御の喪失をもたらし、無制御な細胞増殖を引き起こす可能性がある。p57^KIP2はベックウィズ・ヴィーデマン症候群と関係しており、この疾患は小児期の腫瘍形成リスクの増加によって特徴づけられる^[7]。この遺伝子の機能喪失変異はIMAGe症候群（Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital anomalies）とも関係していることが示されている^[8]。CDKN1C遺伝子は父親由来のアレルがインプリンティング（サイレンシング）されている遺伝子であり、父親由来のDNAのみから構成される全胞状奇胎の細胞ではp57^KIP2の発現がみられない。そのため、p57^KIP2の免疫組織染色を胞状奇胎の診断に利用することができる^[9]。

相互作用

CDKN1Cは次に挙げる因子と相互作用することが示されている。

• LIMK1（英語版）^[10]
• MYBL2（英語版）^[11]
• MyoD（英語版）^[12]
• PCNA^[13]

出典

1. GRCh38: Ensembl release 89: ENSG00000273707、ENSG00000129757 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000037664 - Ensembl, May 2017
3. Human PubMed Reference:
4. Mouse PubMed Reference:
5. “Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)”. 2022年2月12日閲覧。
6. “p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene”. Genes & Development 9 (6): 650–62. (Mar 1995). doi:10.1101/gad.9.6.650. PMID 7729684.
7. “New p57KIP2 mutations in Beckwith-Wiedemann syndrome”. Human Genetics 100 (5–6): 681–3. (Oct 1997). doi:10.1007/s004390050573. PMID 9341892.
8. “Gain of function in CDKN1C”. Nature Genetics 44 (7): 737–8. (Jul 2012). doi:10.1038/ng.2336. PMID 22735584.
9. 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.
10. “p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus”. The Journal of Biological Chemistry 278 (52): 52919–23. (Dec 2003). doi:10.1074/jbc.M309334200. PMID 14530263.
11. “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. (Nov 2003). doi:10.1074/jbc.M308953200. PMID 12947099.
12. “Stabilization of MyoD by direct binding to p57(Kip2)”. The Journal of Biological Chemistry 275 (25): 18767–76. (Jun 2000). doi:10.1074/jbc.M907412199. PMID 10764802.
13. “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. (Feb 1998). Bibcode: 1998PNAS...95.1392W. doi:10.1073/pnas.95.4.1392. PMC 19016. PMID 9465025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC19016/.

関連文献

• “Genes associated with tumor suppression and growth control in the human nervous system”. Cancer and Metastasis Reviews 10 (4): 281–7. (Dec 1991). doi:10.1007/BF00554790. PMID 1786629.
• “Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution”. Genes & Development 9 (6): 639–49. (Mar 1995). doi:10.1101/gad.9.6.639. PMID 7729683.
• “p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene”. Genes & Development 9 (6): 650–62. (Mar 1995). doi:10.1101/gad.9.6.650. PMID 7729684.
• “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. (Apr 1996). Bibcode: 1996PNAS...93.3026M. doi:10.1073/pnas.93.7.3026. PMC 39755. PMID 8610162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC39755/.
• “Genomic organization of the human p57KIP2 gene and its analysis in the G401 Wilms' tumor assay”. Cancer Research 56 (6): 1214–8. (Mar 1996). PMID 8640800.
• “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. (May 1996). doi:10.1007/BF02281873. PMID 8655143.
• “An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome”. Nature Genetics 14 (2): 171–3. (Oct 1996). doi:10.1038/ng1096-171. PMID 8841187.
• “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. (Nov 1996). PMID 8934543.
• “New functional activities for the p21 family of CDK inhibitors”. Genes & Development 11 (7): 847–62. (Apr 1997). doi:10.1101/gad.11.7.847. PMID 9106657.
• “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. (Feb 1998). Bibcode: 1998PNAS...95.1392W. doi:10.1073/pnas.95.4.1392. PMC 19016. PMID 9465025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC19016/.
• “Functional analysis of the p57KIP2 gene mutation in Beckwith-Wiedemann syndrome”. Human Genetics 104 (3): 205–10. (Mar 1999). doi:10.1007/s004390050937. PMID 10323243.
• “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. (Jul 1999). doi:10.1136/jmg.36.7.518. PMC 1734395. PMID 10424811. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734395/.
• “Stabilization of MyoD by direct binding to p57(Kip2)”. The Journal of Biological Chemistry 275 (25): 18767–76. (Jun 2000). doi:10.1074/jbc.M907412199. PMID 10764802.
• “Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors”. Experimental Hematology 29 (4): 490–8. (Apr 2001). doi:10.1016/S0301-472X(01)00619-1. PMID 11301189.
• “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. (Apr 2002). doi:10.1074/jbc.M108747200. PMID 11815601.
• “Induction of p57(KIP2) expression by p73beta”. Proceedings of the National Academy of Sciences of the United States of America 99 (6): 3529–34. (Mar 2002). Bibcode: 2002PNAS...99.3529B. doi:10.1073/pnas.062491899. PMC 122557. PMID 11891335. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC122557/.
• “Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues”. International Journal of Molecular Medicine 9 (4): 373–6. (Apr 2002). doi:10.3892/ijmm.9.4.373. PMID 11891530.
• “Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors”. Oncogene 21 (17): 2741–9. (Apr 2002). doi:10.1038/sj.onc.1205376. PMID 11965547.
• “Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype”. Blood 100 (7): 2572–7. (Oct 2002). doi:10.1182/blood-2001-11-0026. PMID 12239171.

外部リンク

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