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Gene Review

Ccnd3  -  cyclin D3

Rattus norvegicus

Synonyms: G1/S-specific cyclin-D3
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Disease relevance of Ccnd3


High impact information on Ccnd3

  • Substantial evidence suggests that cyclin D1 plays a pivotal role in the control of the hepatocyte cell cycle in response to mitogenic stimuli, whereas the closely related protein cyclin D3 has not been extensively evaluated [3].
  • In quiescent cells, cyclin D3 and cdk4 were cytoplasmatic, whereas cyclin D1 was nuclear [4].
  • Compared with control animals, animals treated with 2-AAF showed increased levels of cdk 4 and cyclin D3 from 12 and 15 hours after PH, respectively, and altered cyclicity in cyclin D3 expression [5].
  • In contrast, cyclin D3 expression coincides with podocyte differentiation and quiescence [6].
  • Activation of endogenous (PRL) or transfected estrogen-responsive genes occurs at the same, higher concentrations of E2 required to promote cell survival, whereas stimulation of cyclin D3 expression and DNA synthesis occur at lower E2 concentrations [7].

Chemical compound and disease context of Ccnd3


Biological context of Ccnd3

  • D-type cyclins including cyclin D1, cyclin D2, and cyclin D3 are cell cycle regulators that promote progression through the early-to-mid G1 phase of the cell cycle [8].
  • The increase in cyclin D3 expression occurred after the propylthiouracil-induced increase in TSH levels and preceded the burst of cell proliferation [1].
  • We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation by chronic stimulation of the TSH/cAMP pathway plays a role in human and experimental hyperproliferative diseases of the thyroid gland [1].
  • Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone-dependence and contact inhibition [1].
  • To investigate the transcription initiation mechanism of the gene encoding cyclin D3, one of the major G1 cyclins to promote the G1/S transition, we cloned the 5' portion of rat cyclin D3 gene and analyzed the promoter region [9].

Anatomical context of Ccnd3


Associations of Ccnd3 with chemical compounds


Physical interactions of Ccnd3

  • Western assays demonstrated, further, that cyclin D3 was complexed with the cyclin dependent-kinases, cdk2 and cdk4, in differentiated L6 cells [10].

Regulatory relationships of Ccnd3


Other interactions of Ccnd3


Analytical, diagnostic and therapeutic context of Ccnd3

  • At 5 hours after hepatectomy, cyclin D3 and cdk4 began to move into the nucleus, and at 13 hours, they were mostly nuclear [4].
  • Mobility shift assays identified proteins in Schwann cell nuclear extracts that formed stable complexes with the cyclin D3 CCAAT promoter element and were disrupted by anti-C/EBPbeta antibody [23].
  • Interestingly, Western blot analysis of protein extracts from RVRT showed the induction of a new 40 kDa protein that cross-reacted with the cyclin D3 antibody [24].


  1. Critical role of cyclin D3 in TSH-dependent growth of thyrocytes and in hyperproliferative diseases of the thyroid gland. Motti, M.L., Boccia, A., Belletti, B., Bruni, P., Troncone, G., Cito, L., Monaco, M., Chiappetta, G., Baldassarre, G., Palombini, L., Fusco, A., Viglietto, G. Oncogene (2003) [Pubmed]
  2. Antiproliferative action of valproate is associated with aberrant expression and nuclear translocation of cyclin D3 during the C6 glioma G1 phase. Bacon, C.L., Gallagher, H.C., Haughey, J.C., Regan, C.M. J. Neurochem. (2002) [Pubmed]
  3. Differential regulation of cyclins D1 and D3 in hepatocyte proliferation. Rickheim, D.G., Nelsen, C.J., Fassett, J.T., Timchenko, N.A., Hansen, L.K., Albrecht, J.H. Hepatology (2002) [Pubmed]
  4. Activation of cdk4 and cdk2 during rat liver regeneration is associated with intranuclear rearrangements of cyclin-cdk complexes. Jaumot, M., Estanyol, J.M., Serratosa, J., Agell, N., Bachs, O. Hepatology (1999) [Pubmed]
  5. Inhibition of in vivo rat liver regeneration by 2-acetylaminofluorene affects the regulation of cell cycle-related proteins. Ohlson, L.C., Koroxenidou, L., Hällström, I.P. Hepatology (1998) [Pubmed]
  6. Differential expression of d-type cyclins in podocytes in vitro and in vivo. Petermann, A., Hiromura, K., Pippin, J., Blonski, M., Couser, W.G., Kopp, J., Mundel, P., Shankland, S.J. Am. J. Pathol. (2004) [Pubmed]
  7. Distinct signaling pathways mediate stimulation of cell cycle progression and prevention of apoptotic cell death by estrogen in rat pituitary tumor PR1 cells. Caporali, S., Imai, M., Altucci, L., Cancemi, M., Caristi, S., Cicatiello, L., Matarese, F., Penta, R., Sarkar, D.K., Bresciani, F., Weisz, A. Mol. Biol. Cell (2003) [Pubmed]
  8. Estrogen activates cyclin-dependent kinases 4 and 6 through induction of cyclin D in rat primary osteoblasts. Fujita, M., Urano, T., Horie, K., Ikeda, K., Tsukui, T., Fukuoka, H., Tsutsumi, O., Ouchi, Y., Inoue, S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  9. Structure and characterization of rat cyclin D3 promoter. Yang, M., Hosokawa, Y., Kaneko, S., Tanaka, M., Nakashima, K. Gene (1996) [Pubmed]
  10. Expression of the positive regulator of cell cycle progression, cyclin D3, is induced during differentiation of myoblasts into quiescent myotubes. Kiess, M., Gill, R.M., Hamel, P.A. Oncogene (1995) [Pubmed]
  11. Cytoplasmic localization of cyclin D3 in seminiferous tubules during testicular development. Kang, M.J., Kim, M.K., Terhune, A., Park, J.K., Kim, Y.H., Koh, G.Y. Exp. Cell Res. (1997) [Pubmed]
  12. Focal adhesion kinase mediates endothelin-induced cyclin D3 expression in rat cultured astrocytes. Koyama, Y., Yoshioka, Y., Shinde, M., Matsuda, T., Baba, A. J. Neurochem. (2004) [Pubmed]
  13. DES action in the thymus: inhibition of cell proliferation and genetic variation. Gould, K.A., Shull, J.D., Gorski, J. Mol. Cell. Endocrinol. (2000) [Pubmed]
  14. Glucocorticoid inhibition of 235-1 rat pituitary tumor cell cycle progression. Delidow, B.C., Wang, M., Bhamidipaty, S.V., Black, L.D. Endocrine (2002) [Pubmed]
  15. Dietary alpha-tocopherol affects differential gene expression in rat testes. Rota, C., Barella, L., Minihane, A.M., Stöcklin, E., Rimbach, G. IUBMB Life (2004) [Pubmed]
  16. Cyclin D3 mediates synthesis of a hyaluronan matrix that is adhesive for monocytes in mesangial cells stimulated to divide in hyperglycemic medium. Ren, J., Hascall, V.C., Wang, A. J. Biol. Chem. (2009) [Pubmed]
  17. Prolactin-induced expression of TATA-less cyclin D3 gene is mediated by Sp1 and AP2. Yang, M., Nomura, H., Hu, Y., Kaneko, S., Kaneko, H., Tanaka, M., Nakashima, K. Biochem. Mol. Biol. Int. (1998) [Pubmed]
  18. Growth factor dependence of progression through G1 and S phases of adult rat hepatocytes in vitro. Evidence of a mitogen restriction point in mid-late G1. Loyer, P., Cariou, S., Glaise, D., Bilodeau, M., Baffet, G., Guguen-Guillouzo, C. J. Biol. Chem. (1996) [Pubmed]
  19. Transforming growth factor-beta 1 inhibits cyclin D1 expression in intestinal epithelial cells. Ko, T.C., Sheng, H.M., Reisman, D., Thompson, E.A., Beauchamp, R.D. Oncogene (1995) [Pubmed]
  20. Fibronectin promotes cell cycle entry in smooth muscle cells in primary culture. Roy, J., Tran, P.K., Religa, P., Kazi, M., Henderson, B., Lundmark, K., Hedin, U. Exp. Cell Res. (2002) [Pubmed]
  21. Microarray analysis of gene expression in proliferating Schwann cells: synergistic response of a specific subset of genes to the mitogenic action of heregulin plus forskolin. Schworer, C.M., Masker, K.K., Wood, G.C., Carey, D.J. J. Neurosci. Res. (2003) [Pubmed]
  22. Differential localization of decidual stathmin during pregnancy in rats. Yoshie, M., Tamura, K., Kogo, H. Placenta (2004) [Pubmed]
  23. Heregulin and forskolin-induced cyclin D3 expression in Schwann cells: role of a CCAAT promoter element and CCAAT enhancer binding protein. Fuentealba, L., Schworer, C., Schroering, A., Rahmatullah, M., Carey, D.J. Glia (2004) [Pubmed]
  24. Temporal expressions of cyclins and cyclin dependent kinases during renal development and compensatory growth. Park, S.K., Kang, S.K., Lee, D.Y., Kang, M.J., Kim, S.H., Koh, G.Y. Kidney Int. (1997) [Pubmed]
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