Cyclin D1

See also: Cyclin D

Cyclin D1
Rendering based on PDB 2W96.
Available structures PDB 2W96, 2W99, 2W9F, 2W9Z
Identifiers
Symbols	CCND1; BCL1; D11S287E; PRAD1; U21B31
External IDs	OMIM: 168461 MGI: 88313 HomoloGene: 1334 GeneCards: CCND1 Gene
Gene Ontology Molecular function • protein kinase activity • protein binding • cyclin-dependent protein kinase regulator activity • enzyme binding • protein kinase binding • protein complex binding Cellular component • cyclin-dependent protein kinase holoenzyme complex • intracellular • nucleus • nucleoplasm • nucleoplasm • cytoplasm • cytosol • cytosol • membrane Biological process • G1 phase of mitotic cell cycle • G1/S transition of mitotic cell cycle • G1/S transition of mitotic cell cycle • S phase of mitotic cell cycle • mitotic cell cycle • re-entry into mitotic cell cycle • liver development • positive regulation of protein phosphorylation • response to DNA damage stimulus • lactation • positive regulation of cell proliferation • response to iron ion • response to X-ray • response to organic nitrogen • response to organic cyclic compound • negative regulation of Wnt receptor signaling pathway • negative regulation of epithelial cell differentiation • endoplasmic reticulum unfolded protein response • organ regeneration • mitotic cell cycle G1/S transition DNA damage checkpoint • response to magnesium ion • response to vitamin E • Leydig cell differentiation • positive regulation of mammary gland epithelial cell proliferation • response to drug • response to estrogen stimulus • fat cell differentiation • response to ethanol • positive regulation of cyclin-dependent protein kinase activity • cell division • response to corticosterone stimulus • response to calcium ion • canonical Wnt receptor signaling pathway • mammary gland alveolus development • response to UV-A • cellular response to protein stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	595	12443
Ensembl	ENSG00000110092	ENSMUSG00000070348
UniProt	P24385	Q3TC96
RefSeq (mRNA)	NM_053056.2	NM_007631.2
RefSeq (protein)	NP_444284.1	NP_031657.1
Location (UCSC)	Chr 11: 69.46 – 69.47 Mb	Chr 7: 152.12 – 152.13 Mb
PubMed search	[1]	[2]

G1/S-specific cyclin-D1 is a protein that in humans is encoded by the CCND1 gene.^[1][2]

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of tumors and may contribute to tumorigenesis.^[3]

Micrograph of cyclin D1 staining in a mantle cell lymphoma.

Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma.

Interactions

Cyclin D1 has been shown to interact with Thyroid hormone receptor beta,^[4] CCNDBP1,^[5] Retinoblastoma protein,^[6][7] Androgen receptor,^[8][9] Cyclin-dependent kinase 4,^{[10][11][12][13][14][15]} Cyclin-dependent kinase 6,^[10][12] TAF1,^[16][6] NEUROD1,^[17] PCNA,^[18][19] Nuclear receptor coactivator 1,^[20] Estrogen receptor alpha^[21] and HDAC3.^[8][4]

See also

• Parathyroid adenoma
• Mantle Cell Lymphoma

References

1. ^ Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A (May 1991). "A novel cyclin encoded by a bcl1-linked candidate oncogene". Nature 350 (6318): 512–5. doi:10.1038/350512a0. PMID 1826542. 
2. ^ Lew DJ, Dulic V, Reed SI (Oct 1991). "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast". Cell 66 (6): 1197–206. doi:10.1016/0092-8674(91)90042-W. PMID 1833066. 
3. ^ "Entrez Gene: CCND1 cyclin D1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=595. 
4. ^ ^{a b} Lin, Huei-Min; Zhao Li, Cheng Sheue-Yann (Aug. 2002). "Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors". J. Biol. Chem. (United States) 277 (32): 28733–41. doi:10.1074/jbc.M203380200. ISSN 0021-9258. PMID 12048199. 
5. ^ Xia, C; Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M (Jul. 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity". J. Biol. Chem. (UNITED STATES) 275 (27): 20942–8. doi:10.1074/jbc.M002598200. ISSN 0021-9258. PMID 10801854. 
6. ^ ^{a b} Siegert, J L; Rushton J J, Sellers W R, Kaelin W G, Robbins P D (Nov. 2000). "Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity". Oncogene (England) 19 (50): 5703–11. doi:10.1038/sj.onc.1203966. ISSN 0950-9232. PMID 11126356. 
7. ^ Dowdy, S F; Hinds P W, Louie K, Reed S I, Arnold A, Weinberg R A (May. 1993). "Physical interaction of the retinoblastoma protein with human D cyclins". Cell (UNITED STATES) 73 (3): 499–511. doi:10.1016/0092-8674(93)90137-F. ISSN 0092-8674. PMID 8490963. 
8. ^ ^{a b} Petre-Draviam, Christin E; Williams Erin B, Burd Craig J, Gladden Andrew, Moghadam Hamed, Meller Jaroslaw, Diehl J Alan, Knudsen Karen E (Jan. 2005). "A central domain of cyclin D1 mediates nuclear receptor corepressor activity". Oncogene (England) 24 (3): 431–44. doi:10.1038/sj.onc.1208200. ISSN 0950-9232. PMID 15558026. 
9. ^ Knudsen, K E; Cavenee W K, Arden K C (May. 1999). "D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability". Cancer Res. (UNITED STATES) 59 (10): 2297–301. ISSN 0008-5472. PMID 10344732. 
10. ^ ^{a b} Sugimoto, M; Nakamura T, Ohtani N, Hampson L, Hampson I N, Shimamoto A, Furuichi Y, Okumura K, Niwa S, Taya Y, Hara E (Nov. 1999). "Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1". Genes Dev. (UNITED STATES) 13 (22): 3027–33. doi:10.1101/gad.13.22.3027. ISSN 0890-9369. PMC 317153. PMID 10580009. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317153. 
11. ^ Serrano, M; Hannon G J, Beach D (Dec. 1993). "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4". Nature (ENGLAND) 366 (6456): 704–7. doi:10.1038/366704a0. ISSN 0028-0836. PMID 8259215. 
12. ^ ^{a b} Lin, J; Jinno S, Okayama H (Apr. 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene (England) 20 (16): 2000–9. doi:10.1038/sj.onc.1204375. ISSN 0950-9232. PMID 11360184. 
13. ^ Taulés, M; Rius E, Talaya D, López-Girona A, Bachs O, Agell N (Dec. 1998). "Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". J. Biol. Chem. (UNITED STATES) 273 (50): 33279–86. doi:10.1074/jbc.273.50.33279. ISSN 0021-9258. PMID 9837900. 
14. ^ Cariou, S; Donovan J C, Flanagan W M, Milic A, Bhattacharya N, Slingerland J M (Aug. 2000). "Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (16): 9042–6. doi:10.1073/pnas.160016897. ISSN 0027-8424. PMC 16818. PMID 10908655. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16818. 
15. ^ Coleman, K G; Wautlet B S, Morrissey D, Mulheron J, Sedman S A, Brinkley P, Price S, Webster K R (Jul. 1997). "Identification of CDK4 sequences involved in cyclin D1 and p16 binding". J. Biol. Chem. (UNITED STATES) 272 (30): 18869–74. doi:10.1074/jbc.272.30.18869. ISSN 0021-9258. PMID 9228064. 
16. ^ Adnane, J; Shao Z, Robbins P D (Jan. 1999). "Cyclin D1 associates with the TBP-associated factor TAF(II)250 to regulate Sp1-mediated transcription". Oncogene (ENGLAND) 18 (1): 239–47. doi:10.1038/sj.onc.1202297. ISSN 0950-9232. PMID 9926939. 
17. ^ Ratineau, Christelle; Petry Mary W, Mutoh Hiroyuki, Leiter Andrew B (Mar. 2002). "Cyclin D1 represses the basic helix-loop-helix transcription factor, BETA2/NeuroD". J. Biol. Chem. (United States) 277 (11): 8847–53. doi:10.1074/jbc.M110747200. ISSN 0021-9258. PMID 11788592. 
18. ^ Matsuoka, S; Yamaguchi M, Matsukage A (Apr. 1994). "D-type cyclin-binding regions of proliferating cell nuclear antigen". J. Biol. Chem. (UNITED STATES) 269 (15): 11030–6. ISSN 0021-9258. PMID 7908906. 
19. ^ Xiong, Y; Zhang H, Beach D (Aug. 1993). "Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation". Genes Dev. (UNITED STATES) 7 (8): 1572–83. doi:10.1101/gad.7.8.1572. ISSN 0890-9369. PMID 8101826. 
20. ^ Zwijsen, R M; Buckle R S, Hijmans E M, Loomans C J, Bernards R (Nov. 1998). "Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1". Genes Dev. (UNITED STATES) 12 (22): 3488–98. doi:10.1101/gad.12.22.3488. ISSN 0890-9369. PMC 317237. PMID 9832502. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317237. 
21. ^ Zwijsen, R M; Wientjens E, Klompmaker R, van der Sman J, Bernards R, Michalides R J (Feb. 1997). "CDK-independent activation of estrogen receptor by cyclin D1". Cell (UNITED STATES) 88 (3): 405–15. doi:10.1016/S0092-8674(00)81879-6. ISSN 0092-8674. PMID 9039267. 

Further reading

• Akita H (2003). "[Prognostic importance of altered expression of cell cycle regulators in lung cancer]". Nippon Rinsho 60 Suppl 5: 267–71. PMID 12101670. 
• Chung DC (2004). "Cyclin D1 in human neuroendocrine: tumorigenesis". Ann. N. Y. Acad. Sci. 1014: 209–17. doi:10.1196/annals.1294.022. PMID 15153436. 
• Jain S, Khuri FR, Shin DM (2004). "Prevention of head and neck cancer: current status and future prospects". Current problems in cancer 28 (5): 265–86. doi:10.1016/j.currproblcancer.2004.05.003. PMID 15375804. 
• Gladden AB, Diehl JA (2006). "Location, location, location: the role of cyclin D1 nuclear localization in cancer". J. Cell. Biochem. 96 (5): 906–13. doi:10.1002/jcb.20613. PMID 16163738. 
• Walker JL, Assoian RK (2006). "Integrin-dependent signal transduction regulating cyclin D1 expression and G1 phase cell cycle progression". Cancer Metastasis Rev. 24 (3): 383–93. doi:10.1007/s10555-005-5130-7. PMID 16258726. 
• Gautschi O, Ratschiller D, Gugger M, et al. (2007). "Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation". Lung Cancer 55 (1): 1–14. doi:10.1016/j.lungcan.2006.09.024. PMID 17070615. 
• Li Z, Wang C, Prendergast GC, Pestell RG (2007). "Cyclin D1 functions in cell migration". Cell Cycle 5 (21): 2440–2. PMID 17106256. 
• Tao Zhang, Breslin MB, Lan MS (2009). "Zinc Finger Transcription Factor INSM1 Interrupts Cyclin D1 and CDK4 Binding and Induces Cell Cycle Arrest". J. Biol. Chem. 284 (9): 5574–81. doi:10.1074/jbc.M808843200. PMC 2645817. PMID 19124461. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2645817. 
• Inaba T, Matsushime H, Valentine M, et al. (1992). "Genomic organization, chromosomal localization, and independent expression of human cyclin D genes". Genomics 13 (3): 565–74. doi:10.1016/0888-7543(92)90126-D. PMID 1386335. 
• Schuuring E, Verhoeven E, Mooi WJ, Michalides RJ (1992). "Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas". Oncogene 7 (2): 355–61. PMID 1532244. 
• Seto M, Yamamoto K, Iida S, et al. (1992). "Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy with t(11;14)(q13;q32) translocation". Oncogene 7 (7): 1401–6. PMID 1535701. 
• Rosenberg CL, Wong E, Petty EM, et al. (1991). "PRAD1, a candidate BCL1 oncogene: mapping and expression in centrocytic lymphoma". Proc. Natl. Acad. Sci. U.S.A. 88 (21): 9638–42. doi:10.1073/pnas.88.21.9638. PMC 52773. PMID 1682919. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=52773. 
• Xiong Y, Connolly T, Futcher B, Beach D (1991). "Human D-type cyclin". Cell 65 (4): 691–9. doi:10.1016/0092-8674(91)90100-D. PMID 1827756. 
• Withers DA, Harvey RC, Faust JB, et al. (1991). "Characterization of a candidate bcl-1 gene". Mol. Cell. Biol. 11 (10): 4846–53. PMC 361453. PMID 1833629. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=361453. 
• Tsujimoto Y, Yunis J, Onorato-Showe L, et al. (1984). "Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation". Science 224 (4656): 1403–6. doi:10.1126/science.6610211. PMID 6610211. 
• Hall M, Bates S, Peters G (1995). "Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins". Oncogene 11 (8): 1581–8. PMID 7478582. 
• Tassan JP, Jaquenoud M, Léopold P, et al. (1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8871–5. doi:10.1073/pnas.92.19.8871. PMC 41069. PMID 7568034. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=41069. 
• Fornaro M, Dell'Arciprete R, Stella M, et al. (1995). "Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas". Int. J. Cancer 62 (5): 610–8. doi:10.1002/ijc.2910620520. PMID 7665234. 
• Motokura T, Arnold A (1993). "PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint". Genes Chromosomes Cancer 7 (2): 89–95. doi:10.1002/gcc.2870070205. PMID 7687458.