Cyclin D1

Cyclin D1
Cyclin D1

Rendering based on PDB 2W96.
Symbols CCND1; BCL1; D11S287E; PRAD1; U21B31
External IDs OMIM168461 MGI88313 HomoloGene1334 GeneCards: CCND1 Gene
RNA expression pattern
PBB GE CCND1 208712 at tn.png
PBB GE CCND1 208711 s at tn.png
More reference expression data
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.



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


  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". 
  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. 
  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. 
  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. 
  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

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