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Gene Review

Ccnd3  -  cyclin D3

Mus musculus

Synonyms: 9230106B05Rik, AA682053, AL024085, AW146355, C78795, ...
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Disease relevance of Ccnd3


High impact information on Ccnd3


Chemical compound and disease context of Ccnd3

  • Cyclin D3 messenger RNA (CcnD3 mRNA) stability decreases rapidly when murine T lymphoma cells are treated with the synthetic glucocorticoid dexamethasone [10].
  • Immunoblot analysis of cyclin D3 expression in C6 glioma indicated the racemate and S-pentyl-4-yn-VPA to induce dose-dependent up-regulation of this protein, similar to that associated with G1-phase cell cycle arrest mediated by VPA, whereas R-pentyl-4-yn-VPA was without effect [11].

Biological context of Ccnd3


Anatomical context of Ccnd3

  • Through a screen aimed at identifying genes that are specifically upregulated in embryomic stem (ES) cells but not primitive ectoderm, we identified cyclin D3 [16].
  • Cyclin D3-associated kinase activity was detected in immature, but not adult, testes and ovaries [13].
  • In the adult testis, cyclin D3 was also expressed in terminally differentiating spermatids [13].
  • In the early stages of postnatal testicular development, cyclin D3 protein was detected in spermatogonia and Leydig cells [13].
  • Unexpectedly, cyclin D3 and CDK4 pRb kinase activity remained high after 3T3-L1 cells completed their mitotic division and was still readily detectable in mature adipocytes [17].

Associations of Ccnd3 with chemical compounds

  • When CHX was treated alone, cyclin D3, but not cyclin D1, mRNA was immediately superinduced [15].
  • Cells transformed with Cdk4 expression vectors, with or without cyclin D3 expression vectors, also undergo G0 arrest in the presence of dexamethasone [18].
  • The other isolated cDNAs encode genes that have been previously described in other contexts: 1-4 (cyclin D3); 2-10 (pyruvate kinase); 2-12 (glutathione S-transferase); and 2-17 (GLUT 3) [3].
  • To define the role of cyclin D3 in productive infection, the ICP0 binding site for cyclin D3 was mapped and mutagenized by substitution of aspartic acid codon 199 with the alanine codon [9].
  • Levels and interactions of p27, cyclin D3, and CDK4 during the formation and maintenance of the corpus luteum in mice [19].

Physical interactions of Ccnd3

  • In uninduced cells cyclin D3 complexes with pRB and E2F are barely detected [20].
  • Our studies examined the effects of p27(kip1) and p21(cip1) on the assembly and activity of cyclin D3-cdk4 complexes and determined the composition of the cyclin D3 pool in cells containing and lacking these cyclin-dependent kinase inhibitors [21].

Regulatory relationships of Ccnd3


Other interactions of Ccnd3

  • Cdk6 is the major catalytic partner for cyclin D3 in ES cells and exhibits robust pRb kinase activity that is downregulated during the early stages of ES embryoid body differentiation [16].
  • Cdk6-cyclin D3 activity in murine ES cells is resistant to inhibition by p16(INK4a) [16].
  • Our data suggest that Cdk6-cyclin D3 activity in other cell types, including tumors, may also be refractory to p16-mediated growth inhibition and raises the possibility of additional specificity within the INK4 family [16].
  • In isoleucine-deprived cells, which are growth arrested but do not differentiate, the steady state mRNA levels of genes Rex 2, Rex 3, pyruvate kinase and GLUT 3 are not reduced, in contrast to cyclin D3 and glutathione S-transferase [3].
  • In contrast, cyclin D3 exhibits lower mRNA expression in F9 RARgamma-/- and RARalpha-/- stem cells, and this mRNA is not decreased by RACT treatment [3].

Analytical, diagnostic and therapeutic context of Ccnd3


  1. Development of mice expressing a single D-type cyclin. Ciemerych, M.A., Kenney, A.M., Sicinska, E., Kalaszczynska, I., Bronson, R.T., Rowitch, D.H., Gardner, H., Sicinski, P. Genes Dev. (2002) [Pubmed]
  2. Cyclin D2 overexpression in transgenic mice induces thymic and epidermal hyperplasia whereas cyclin D3 expression results only in epidermal hyperplasia. Rodriguez-Puebla, M.L., LaCava, M., Miliani De Marval, P.L., Jorcano, J.L., Richie, E.R., Conti, C.J. Am. J. Pathol. (2000) [Pubmed]
  3. Characterization of genes which exhibit reduced expression during the retinoic acid-induced differentiation of F9 teratocarcinoma cells: involvement of cyclin D3 in RA-mediated growth arrest. Faria, T.N., LaRosa, G.J., Wilen, E., Liao, J., Gudas, L.J. Mol. Cell. Endocrinol. (1998) [Pubmed]
  4. Control of Müller glial cell proliferation and activation following retinal injury. Dyer, M.A., Cepko, C.L. Nat. Neurosci. (2000) [Pubmed]
  5. Cyclin D3 promotes adipogenesis through activation of peroxisome proliferator-activated receptor gamma. Sarruf, D.A., Iankova, I., Abella, A., Assou, S., Miard, S., Fajas, L. Mol. Cell. Biol. (2005) [Pubmed]
  6. A unique function for cyclin D3 in early B cell development. Cooper, A.B., Sawai, C.M., Sicinska, E., Powers, S.E., Sicinski, P., Clark, M.R., Aifantis, I. Nat. Immunol. (2006) [Pubmed]
  7. Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas. Miyatake, S., Nakano, H., Park, S.Y., Yamazaki, T., Takase, K., Matsushime, H., Kato, A., Saito, T. J. Exp. Med. (1995) [Pubmed]
  8. Cell cycle regulation and apoptosis. King, K.L., Cidlowski, J.A. Annu. Rev. Physiol. (1998) [Pubmed]
  9. A single amino acid substitution in the cyclin D binding domain of the infected cell protein no. 0 abrogates the neuroinvasiveness of herpes simplex virus without affecting its ability to replicate. Van Sant, C., Kawaguchi, Y., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  10. Glucocorticoid-mediated destabilization of cyclin D3 mRNA involves RNA-protein interactions in the 3'-untranslated region of the mRNA. Garcia-Gras, E.A., Chi, P., Thompson, E.A. J. Biol. Chem. (2000) [Pubmed]
  11. Differential enantioselective effects of pentyl-4-yn-valproate on spatial learning in the rat, and neurite outgrowth and cyclin D3 expression in vitro. O'Loinsigh, E.D., Gherardini, L.M., Gallagher, H.C., Foley, A.G., Murphy, K.J., Regan, C.M. J. Neurochem. (2004) [Pubmed]
  12. Cyclin D3 compensates for loss of cyclin D2 in mouse B-lymphocytes activated via the antigen receptor and CD40. Lam, E.W., Glassford, J., Banerji, L., Thomas, N.S., Sicinski, P., Klaus, G.G. J. Biol. Chem. (2000) [Pubmed]
  13. Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis. Zhang, Q., Wang, X., Wolgemuth, D.J. Endocrinology (1999) [Pubmed]
  14. G1-phase regulators, cyclin D1, cyclin D2, and cyclin D3: up-regulation at gastrulation and dynamic expression during neurulation. Wianny, F., Real, F.X., Mummery, C.L., Van Rooijen, M., Lahti, J., Samarut, J., Savatier, P. Dev. Dyn. (1998) [Pubmed]
  15. Estrogen-induced cyclin D1 and D3 gene expressions during mouse uterine cell proliferation in vivo: differential induction mechanism of cyclin D1 and D3. Geum, D., Sun, W., Paik, S.K., Lee, C.C., Kim, K. Mol. Reprod. Dev. (1997) [Pubmed]
  16. Cdk6-cyclin D3 activity in murine ES cells is resistant to inhibition by p16(INK4a). Faast, R., White, J., Cartwright, P., Crocker, L., Sarcevic, B., Dalton, S. Oncogene (2004) [Pubmed]
  17. Regulation of cyclin-dependent kinase 4 during adipogenesis involves switching of cyclin D subunits and concurrent binding of p18INK4c and p27Kip1. Phelps, D.E., Xiong, Y. Cell Growth Differ. (1998) [Pubmed]
  18. c-Myc and cyclin D3 (CcnD3) genes are independent targets for glucocorticoid inhibition of lymphoid cell proliferation. Rhee, K., Bresnahan, W., Hirai, A., Hirai, M., Thompson, E.A. Cancer Res. (1995) [Pubmed]
  19. Levels and interactions of p27, cyclin D3, and CDK4 during the formation and maintenance of the corpus luteum in mice. Hampl, A., Pacherník, J., Dvorák, P. Biol. Reprod. (2000) [Pubmed]
  20. Suppression of cyclin-dependent kinase 4 during induced differentiation of erythroleukemia cells. Kiyokawa, H., Richon, V.M., Rifkind, R.A., Marks, P.A. Mol. Cell. Biol. (1994) [Pubmed]
  21. Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1). Bagui, T.K., Jackson, R.J., Agrawal, D., Pledger, W.J. Mol. Cell. Biol. (2000) [Pubmed]
  22. Sequestration of pRb by cyclin D3 causes intranuclear reorganization of lamin A/C during muscle cell differentiation. Mariappan, I., Parnaik, V.K. Mol. Biol. Cell (2005) [Pubmed]
  23. Stem cell factor/c-kit up-regulates cyclin D3 and promotes cell cycle progression via the phosphoinositide 3-kinase/p70 S6 kinase pathway in spermatogonia. Feng, L.X., Ravindranath, N., Dym, M. J. Biol. Chem. (2000) [Pubmed]
  24. Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth. Kushner, J.A., Ciemerych, M.A., Sicinska, E., Wartschow, L.M., Teta, M., Long, S.Y., Sicinski, P., White, M.F. Mol. Cell. Biol. (2005) [Pubmed]
  25. Tumor induction by an Lck-MyrAkt transgene is delayed by mechanisms controlling the size of the thymus. Malstrom, S., Tili, E., Kappes, D., Ceci, J.D., Tsichlis, P.N. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  26. Cyclin D3 accumulation and activity integrate and rank the comitogenic pathways of thyrotropin and insulin in thyrocytes in primary culture. Van Keymeulen, A., Bartek, J., Dumont, J.E., Roger, P.P. Oncogene (1999) [Pubmed]
  27. Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy. Das, S.K., Lim, H., Paria, B.C., Dey, S.K. J. Mol. Endocrinol. (1999) [Pubmed]
  28. The positive nuclear staining observed with monoclonal antibody against PRAD1/cyclin D1 correlates with mRNA expression in mantle cell lymphoma. Kuroda, H., Komatsu, H., Nakamura, S., Niitsu, Y., Takahashi, T., Ueda, R., Seto, M. Jpn. J. Cancer Res. (1995) [Pubmed]
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