Cyclin D1

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See also: Cyclin D
Cyclin D1
Protein CCND1 PDB 2W96.png
Rendering based on PDB 2W96.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols CCND1 ; BCL1; D11S287E; PRAD1; U21B31
External IDs OMIM168461 MGI88313 HomoloGene1334 ChEMBL: 3610 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 P25322
RefSeq (mRNA) NM_053056 NM_007631
RefSeq (protein) NP_444284 NP_031657
Location (UCSC) Chr 11:
69.46 – 69.47 Mb
Chr 7:
144.93 – 144.94 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 CDKs (Cyclin-dependent kinase). 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 found to be overexpressed in breast carcinoma. Its potential use as a biomarker was suggested.[4]


Cyclin D1 has been shown to interact with:

See also[edit]


  1. ^ Motokura T, Bloom T, Kim HG, Jüppner H, Ruderman JV, Kronenberg HM et al. (May 1991). "A novel cyclin encoded by a bcl1-linked candidate oncogene". Nature 350 (6318): 512–5. doi:10.1038/350512a0. PMID 1826542.  Vancouver style error (help)
  2. ^ Lew DJ, Dulić V, Reed SI (October 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.  Vancouver style error (help)
  3. ^ "Entrez Gene: CCND1 cyclin D1". 
  4. ^ He Y, Liu Z, Qiao C, Xu M, Yu J, Li G (Jan 2014). "Expression and significance of Wnt signaling components and their target genes in breast carcinoma". Mol Med Rep 9 (1): 137–43. doi:10.3892/mmr.2013.1774. PMID 24190141. 
  5. ^ Reutens AT, Fu M, Wang C, Albanese C, McPhaul MJ, Sun Z et al. (May 2001). "Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner". Mol. Endocrinol. 15 (5): 797–811. doi:10.1210/mend.15.5.0641. PMID 11328859. 
  6. ^ a b Petre-Draviam CE, Williams EB, Burd CJ, Gladden A, Moghadam H, Meller J et al. (January 2005). "A central domain of cyclin D1 mediates nuclear receptor corepressor activity". Oncogene 24 (3): 431–44. doi:10.1038/sj.onc.1208200. PMID 15558026. 
  7. ^ Knudsen KE, Cavenee WK, Arden KC (May 1999). "D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability". Cancer Res. 59 (10): 2297–301. PMID 10344732. 
  8. ^ a b Wang C, Fan S, Li Z, Fu M, Rao M, Ma Y et al. (Aug 2005). "Cyclin D1 antagonizes BRCA1 repression of estrogen receptor alpha activity". Cancer Res. 65 (15): 6557–67. doi:10.1158/0008-5472.CAN-05-0486. PMID 16061635. 
  9. ^ a b Casimiro MC, Wang C, Li Z, Di Sante G, Willmart NE, Addya S et al. (Sep 2013). "Cyclin D1 determines estrogen signaling in the mammary gland in vivo". Mol. Endocrinol. 27 (9): 1415–28. doi:10.1210/me.2013-1065. PMC 3753428. PMID 23864650. 
  10. ^ Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S et al. (July 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity". J. Biol. Chem. 275 (27): 20942–8. doi:10.1074/jbc.M002598200. PMID 10801854. 
  11. ^ a b Sugimoto M, Nakamura T, Ohtani N, Hampson L, Hampson IN, Shimamoto A et al. (November 1999). "Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1)". Genes Dev. 13 (22): 3027–33. doi:10.1101/gad.13.22.3027. PMC 317153. PMID 10580009. 
  12. ^ Serrano M, Hannon GJ, Beach D (December 1993). "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4". Nature 366 (6456): 704–7. doi:10.1038/366704a0. PMID 8259215. 
  13. ^ a b Lin J, Jinno S, Okayama H (April 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene 20 (16): 2000–9. doi:10.1038/sj.onc.1204375. PMID 11360184. 
  14. ^ Taulés M, Rius E, Talaya D, López-Girona A, Bachs O, Agell N (December 1998). "Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". J. Biol. Chem. 273 (50): 33279–86. doi:10.1074/jbc.273.50.33279. PMID 9837900.  Vancouver style error (help)
  15. ^ Cariou S, Donovan JC, Flanagan WM, Milic A, Bhattacharya N, Slingerland JM (August 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. 97 (16): 9042–6. doi:10.1073/pnas.160016897. PMC 16818. PMID 10908655. 
  16. ^ Coleman KG, Wautlet BS, Morrissey D, Mulheron J, Sedman SA, Brinkley P et al. (July 1997). "Identification of CDK4 sequences involved in cyclin D1 and p16 binding". J. Biol. Chem. 272 (30): 18869–74. doi:10.1074/jbc.272.30.18869. PMID 9228064. 
  17. ^ Neuman E, Ladha MH, Lin N, Upton TM, Miller SJ, DiRenzo J et al. (Sep 1997). "Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4". Mol. Cell. Biol. 17 (9): 5338–47. PMC 232384. PMID 9271411. 
  18. ^ Zwijsen RM, Wientjens E, Klompmaker R, van der Sman J, Bernards R, Michalides RJ (February 1997). "CDK-independent activation of estrogen receptor by cyclin D1". Cell 88 (3): 405–15. doi:10.1016/s0092-8674(00)81879-6. PMID 9039267. 
  19. ^ a b Lin HM, Zhao L, Cheng SY (August 2002). "Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors". J. Biol. Chem. 277 (32): 28733–41. doi:10.1074/jbc.M203380200. PMID 12048199. 
  20. ^ Fu M, Rao M, Bouras T, Wang C, Wu K, Zhang X et al. (July 2006). "Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment". J. Biol. Chem. 280 (17): 16934–41. doi:10.1074/jbc.M500403200. PMID 15713663.  Check date values in: |year= / |date= mismatch (help)
  21. ^ Ratineau C, Petry MW, Mutoh H, Leiter AB (March 2002). "Cyclin D1 represses the basic helix-loop-helix transcription factor, BETA2/NeuroD". J. Biol. Chem. 277 (11): 8847–53. doi:10.1074/jbc.M110747200. PMID 11788592. 
  22. ^ Zwijsen RM, Buckle RS, Hijmans EM, Loomans CJ, Bernards R (November 1998). "Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1". Genes Dev. 12 (22): 3488–98. doi:10.1101/gad.12.22.3488. PMC 317237. PMID 9832502. 
  23. ^ Wang C, Li Z, Lu Y, Du R, Katiyar S, Yang J et al. (July 2006). "Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function". Proc. Natl. Acad. Sci. U.S.A. 103 (31): 11567–72. doi:10.1073/pnas.0603363103. PMC 1518800. PMID 16864783. 
  24. ^ Fu M, Wang C, Rao M, Wu X, Bouras T, Zhang X et al. (Aug 2005). "Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism". J. Biol. Chem. 280 (33): 29728–42. doi:10.1074/jbc.M503188200. PMID 15951563. 
  25. ^ Meng H, Tian L, Zhou J, Li Z, Jiao X, Li WW et al. (Jan 2011). "PACSIN 2 represses cellular migration through direct association with cyclin D1 but not its alternate splice form cyclin D1b". Cell Cycle 10 (1): 73–81. doi:10.4161/cc.10.1.14243. PMC 3048077. PMID 21200149. 
  26. ^ Matsuoka S, Yamaguchi M, Matsukage A (April 1994). "D-type cyclin-binding regions of proliferating cell nuclear antigen". J. Biol. Chem. 269 (15): 11030–6. PMID 7908906. 
  27. ^ Xiong Y, Zhang H, Beach D (August 1993). "Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation". Genes Dev. 7 (8): 1572–83. doi:10.1101/gad.7.8.1572. PMID 8101826. 
  28. ^ Wang C, Pattabiraman N, Zhou JN, Fu M, Sakamaki T, Albanese C et al. (Sep 2003). "Cyclin D1 repression of peroxisome proliferator-activated receptor gamma expression and transactivation". Mol. Cell. Biol. 23 (17): 6159–73. doi:10.1128/mcb.23.17.6159-6173.2003. PMC 180960. PMID 12917338. 
  29. ^ Li Z, Jiao X, Wang C, Shirley LA, Elsaleh H, Dahl O et al. (November 2010). "Alternative cyclin D1 splice forms differentially regulate the DNA damage response". Cancer Res. 70 (21): 8802–11. doi:10.1158/0008-5472.CAN-10-0312. PMC 2970762. PMID 20940395. 
  30. ^ a b Siegert JL, Rushton JJ, Sellers WR, Kaelin WG, Robbins PD (November 2000). "Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity". Oncogene 19 (50): 5703–11. doi:10.1038/sj.onc.1203966. PMID 11126356. 
  31. ^ Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA (May 1993). "Physical interaction of the retinoblastoma protein with human D cyclins". Cell 73 (3): 499–511. doi:10.1016/0092-8674(93)90137-f. PMID 8490963. 
  32. ^ Adnane J, Shao Z, Robbins PD (January 1999). "Cyclin D1 associates with the TBP-associated factor TAF(II)250 to regulate Sp1-mediated transcription". Oncogene 18 (1): 239–47. doi:10.1038/sj.onc.1202297. PMID 9926939. 

Further reading[edit]