Cyclin D3

Cyclin D3
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3G33​
Identifiers
Symbol	CCND3
External IDs	OMIM: 123834 MGI: 88315 HomoloGene: 20419 ChEMBL: 2422 GeneCards: CCND3 Gene
Gene ontology Molecular function • cyclin-dependent protein serine/threonine kinase activity • protein binding • protein kinase binding Cellular component • cyclin-dependent protein kinase holoenzyme complex • nucleus • cytoplasm • membrane Biological process • positive regulation of protein phosphorylation • cell cycle • signal transduction • T cell proliferation • positive regulation of cyclin-dependent protein serine/threonine kinase activity • cell division Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	896	12445
Ensembl	ENSG00000112576	ENSMUSG00000034165
UniProt	P30281	P30282
RefSeq (mRNA)	NM_001136017	NM_001081635
RefSeq (protein)	NP_001129489	NP_001075104
Location (UCSC)	Chr 6: 41.93 – 42.05 Mb	Chr 17: 47.51 – 47.6 Mb
PubMed search

G1/S-specific cyclin-D3 is a protein that in humans is encoded by the CCND3 gene.^[1]

Function

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through 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 activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation.^[2]

Clinical significance

Mutations in CCND3 are implicated in cases of breast cancer.^[3]

Interactions

Cyclin D3 has been shown to interact with:

• AKAP8,^[4]
• CDC2L1,^[5]
• CDKN1B,^[6][7][8]
• CRABP2,^[9]
• Cyclin-dependent kinase 4,^[4][6][7][8]
• Cyclin-dependent kinase 6,^[7][10]
• EIF3K,^[11] and
• Retinoic acid receptor alpha.^[9]

See also

• Cyclin
• Cyclin D

References

1. Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT (August 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.
2. "Entrez Gene: CCND3 cyclin D3".
3. "Comprehensive molecular portraits of human breast tumours". Nature (Nature Publishing Group) 490 (7418): 61–70. 2012. doi:10.1038/nature11412. PMC 3465532. PMID 23000897.
4. Arsenijevic T, Degraef C, Dumont JE, Roger PP, Pirson I (2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. 378 (Pt 2): 673–9. doi:10.1042/BJ20031765. PMC 1223988. PMID 14641107.
5. Zhang S, Cai M, Zhang S, Xu S, Chen S, Chen X, Chen C, Gu J (2002). "Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3". J. Biol. Chem. 277 (38): 35314–22. doi:10.1074/jbc.M202179200. PMID 12082095.
6. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
7. Lin J, Jinno S, Okayama H (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.
8. Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology 140 (6): 2790–800. doi:10.1210/endo.140.6.6756. PMID 10342870.
9. Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L (2003). "Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II". J. Biol. Chem. 278 (8): 6355–62. doi:10.1074/jbc.M210697200. PMID 12482873.
10. Meyerson M, Harlow E (1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Mol. Cell. Biol. 14 (3): 2077–86. PMC 358568. PMID 8114739.
11. Shen X, Yang Y, Liu W, Sun M, Jiang J, Zong H, Gu J (2004). "Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3". FEBS Lett. 573 (1-3): 139–46. doi:10.1016/j.febslet.2004.07.071. PMID 15327989.

Further reading

• Motokura T, Keyomarsi K, Kronenberg HM, Arnold A (1992). "Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene". J. Biol. Chem. 267 (28): 20412–5. PMID 1383201.
• Xiong Y, Menninger J, Beach D, Ward DC (1992). "Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins". Genomics 13 (3): 575–84. doi:10.1016/0888-7543(92)90127-E. PMID 1386336.
• Motokura T, Yi HF, Kronenberg HM, McBride OW, Arnold A (1992). "Assignment of the human cyclin D3 gene (CCND3) to chromosome 6p----q13". Cytogenet. Cell Genet. 61 (1): 5–7. doi:10.1159/000133359. PMID 1387066.
• Matsuoka S, Yamaguchi M, Matsukage A (1994). "D-type cyclin-binding regions of proliferating cell nuclear antigen". J. Biol. Chem. 269 (15): 11030–6. PMID 7908906.
• Meyerson M, Harlow E (1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Mol. Cell. Biol. 14 (3): 2077–86. PMC 358568. PMID 8114739.
• Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA (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.
• Brooks AR, Shiffman D, Chan CS, Brooks EE, Milner PG (1996). "Functional analysis of the human cyclin D2 and cyclin D3 promoters". J. Biol. Chem. 271 (15): 9090–9. doi:10.1074/jbc.271.15.9090. PMID 8621559.
• Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffman I, Reed SI, Kimchi A (1996). "Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest". Mol. Cell. Biol. 16 (7): 3934–44. PMC 231390. PMID 8668211.
• Hirai H, Sherr CJ (1996). "Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1". Mol. Cell. Biol. 16 (11): 6457–67. PMC 231647. PMID 8887674.
• Doglioni C, Chiarelli C, Macrí E, Dei Tos AP, Meggiolaro E, Dalla Palma P, Barbareschi M (1998). "Cyclin D3 expression in normal, reactive and neoplastic tissues". J. Pathol. 185 (2): 159–66. doi:10.1002/(SICI)1096-9896(199806)185:2<159::AID-PATH73>3.0.CO;2-0. PMID 9713342.
• Gómez Lahoz E, Liegeois NJ, Zhang P, Engelman JA, Horner J, Silverman A, Burde R, Roussel MF, Sherr CJ, Elledge SJ, DePinho RA (1999). "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Mol. Cell. Biol. 19 (1): 353–63. doi:10.1128/mcb.19.1.353. PMC 83893. PMID 9858559.
• Gabrielli BG, Sarcevic B, Sinnamon J, Walker G, Castellano M, Wang XQ, Ellem KA (1999). "A cyclin D-Cdk4 activity required for G2 phase cell cycle progression is inhibited in ultraviolet radiation-induced G2 phase delay". J. Biol. Chem. 274 (20): 13961–9. doi:10.1074/jbc.274.20.13961. PMID 10318807.
• Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology 140 (6): 2790–800. doi:10.1210/endo.140.6.6756. PMID 10342870.
• Bartkova J, Rajpert-de Meyts E, Skakkebaek NE, Bartek J (1999). "D-type cyclins in adult human testis and testicular cancer: relation to cell type, proliferation, differentiation, and malignancy". J. Pathol. 187 (5): 573–81. doi:10.1002/(SICI)1096-9896(199904)187:5<573::AID-PATH289>3.0.CO;2-H. PMID 10398124.
• Jones CJ, Kipling D, Morris M, Hepburn P, Skinner J, Bounacer A, Wyllie FS, Ivan M, Bartek J, Wynford-Thomas D, Bond JA (2000). "Evidence for a telomere-independent "clock" limiting RAS oncogene-driven proliferation of human thyroid epithelial cells". Mol. Cell. Biol. 20 (15): 5690–9. doi:10.1128/MCB.20.15.5690-5699.2000. PMC 86042. PMID 10891505.
• Sansal I, Dupont E, Toru D, Evrard C, Rouget P (2000). "NPDC-1, a regulator of neural cell proliferation and differentiation, interacts with E2F-1, reduces its binding to DNA and modulates its transcriptional activity". Oncogene 19 (43): 5000–9. doi:10.1038/sj.onc.1203843. PMID 11042687.
• Fink JR, LeBien TW (2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Exp. Hematol. 29 (4): 490–8. doi:10.1016/S0301-472X(01)00619-1. PMID 11301189.
• Lin J, Jinno S, Okayama H (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.
• Bartkova J, Thullberg M, Slezak P, Jaramillo E, Rubio C, Thomassen LH, Bartek J (2001). "Aberrant expression of G1-phase cell cycle regulators in flat and exophytic adenomas of the human colon". Gastroenterology 120 (7): 1680–8. doi:10.1053/gast.2001.24880. PMID 11375949.