The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CCND3  -  cyclin D3

Homo sapiens

Synonyms: G1/S-specific cyclin-D3
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CCND3


High impact information on CCND3

  • Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1 [5].
  • In thyroid tumors and cell lines, cyclin D3 expression was associated with cytoplasmic localization of p27 [6].
  • Moreover, expression of cyclin D3 in thyroid carcinoma cells induced cytoplasmic retention of cotransfected p27 and rescued p27-imposed growth arrest [6].
  • Cleaved Rb bound cyclin D3 and inhibited the transcriptional activity of E2F-1, but failed to bind to the regulatory protein MDM2, which has been implicated in apoptosis [7].
  • Here, we show that the positive cell cycle regulator cyclin D3 [Matsushime H., Roussel M. F., Ashmun, R. A. & Sherr, C. J. (1991) Cell 65, 701-713] interacts with the death enzyme Caspase 2 [Wang, L., Miura, M., Bergeron, L., Zhu, H. & Yuan, J. (1994) Cell 78, 739-750] [8].

Chemical compound and disease context of CCND3

  • Treatment of LCL with LY294002 causes a reduction of the expression of both cyclin D2 and cyclin D3, two key cyclins required for cell cycle progression but does not affect the expression of the EBV latent genes, EBNA2A or LMP-1 [9].
  • The expression of cyclin D3 was studied immunohistochemically in archival formalin-fixed, paraffin-embedded specimens from normal organs obtained from three autopsy cases and 237 human primary pulmonary carcinomas [10].

Biological context of CCND3


Anatomical context of CCND3

  • Induction of p57(Kip2) resulted in increased association of cdk6 with cyclin D3, without receptor-mediated T cell stimulation [16].
  • In contrast to cyclins D1 and D2, cyclin D3 was (i) ubiquitously expressed among a panel of 70 human cultured cell types; (ii) strongly upregulated upon induction of HL-60 leukaemia cells to differentiate; and (iii) accumulated to high levels in a wide range of quiescent cell types in mouse and human differentiated tissues [17].
  • In normal adult tissues, cyclin D3 showed two patterns of distribution: in lymphoid tissues it was expressed in proliferative compartments, while in most other tissues it was expressed by terminally differentiated/quiescent cells [18].
  • In soft tissue neoplasms, cyclin D3 was consistently expressed in some tumours, such as stromal tumours of the gastrointestinal tract and embryonal rhabdomyosarcomas [18].
  • In normal testis, the cell type-restricted expression patterns were dominated by high levels of cyclin D3 in quiescent Leydig cells and the lack of any D-type cyclin in the germ cells, the latter possibly representing the only example of normal mammalian cells proliferating in the absence of these cyclins [19].

Associations of CCND3 with chemical compounds


Physical interactions of CCND3

  • We found that cyclin D3 specifically interacted with eIF3k through its C-terminal domain [25].
  • Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction [26].
  • Third, recombinant E2F1 binds with high affinity to the cyclin D3 promoter in vitro [27].
  • These data suggest that IL-4 controls B cell proliferation by action during at least two steps of the regulation of the cell cycle, cyclin D3/cdk6 complex regulation and p27 inhibitor expression [28].
  • PLC beta1 is a well-known example, given that it has been shown that only the enzyme located in the nucleus targets the cyclin D3/cdk4 complex, playing, in turn, a key role in the control of normal progression through the G1 phase of the cell cycle [29].

Co-localisations of CCND3


Regulatory relationships of CCND3


Other interactions of CCND3

  • Interestingly, cyclin D3 and cdk4 selectively interact with phosphorylated p27(kip1) in BL40 cells [3].
  • Confocal microscopy indicated that cyclin D3 overexpression was limited to areas of IE62 production, whereas cyclin B1 expression was irregular across the VZV plaque [34].
  • CONCLUSION: The results provide additional insight into the mechanism of G1-S cell cycle checkpoints deregulation during stepwise pancreatic duct cell carcinogenesis, and suggest a p16-independent role for cyclin D3 in deregulating the G1 cell cycle checkpoints during early stages of pancreatic duct cell carcinogenesis [35].
  • In most cases (39/46) overexpression of cyclin D3 and cyclin E was mutually exclusive possibly reflecting different underlying pathways inducing deregulated expression of these cyclins [36].
  • The linearity of the RB1 pathway was clearer as only 1 of 34 DLCLs showed aberration of more than one of the components cyclin D3, p16INK4A, and pRB [37].

Analytical, diagnostic and therapeutic context of CCND3


  1. Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas. Büschges, R., Weber, R.G., Actor, B., Lichter, P., Collins, V.P., Reifenberger, G. Brain Pathol. (1999) [Pubmed]
  2. Molecular classification of multiple myeloma: a distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations. Agnelli, L., Bicciato, S., Mattioli, M., Fabris, S., Intini, D., Verdelli, D., Baldini, L., Morabito, F., Callea, V., Lombardi, L., Neri, A. J. Clin. Oncol. (2005) [Pubmed]
  3. Posttranslational modifications of p27kip1 determine its binding specificity to different cyclins and cyclin-dependent kinases in vivo. Zhang, W., Bergamaschi, D., Jin, B., Lu, X. Blood (2005) [Pubmed]
  4. Cyclin D3 expression in melanoma cells is regulated by adhesion-dependent phosphatidylinositol 3-kinase signaling and contributes to G1-S progression. Spofford, L.S., Abel, E.V., Boisvert-Adamo, K., Aplin, A.E. J. Biol. Chem. (2006) [Pubmed]
  5. Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Brennan, P., Babbage, J.W., Burgering, B.M., Groner, B., Reif, K., Cantrell, D.A. Immunity (1997) [Pubmed]
  6. Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells. Baldassarre, G., Belletti, B., Bruni, P., Boccia, A., Trapasso, F., Pentimalli, F., Barone, M.V., Chiappetta, G., Vento, M.T., Spiezia, S., Fusco, A., Viglietto, G. J. Clin. Invest. (1999) [Pubmed]
  7. Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis. Jänicke, R.U., Walker, P.A., Lin, X.Y., Porter, A.G. EMBO J. (1996) [Pubmed]
  8. Cyclin D3 activates Caspase 2, connecting cell proliferation with cell death. Mendelsohn, A.R., Hamer, J.D., Wang, Z.B., Brent, R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells. Brennan, P., Mehl, A.M., Jones, M., Rowe, M. Oncogene (2002) [Pubmed]
  10. Immunohistochemistry of cyclin D3 in pulmonary carcinomas. Usuda, H., Saito, T., Emura, I., Naito, M. Virchows Arch. (1996) [Pubmed]
  11. Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts. Won, K.A., Xiong, Y., Beach, D., Gilman, M.Z. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  12. Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Fu, K., Weisenburger, D.D., Greiner, T.C., Dave, S., Wright, G., Rosenwald, A., Chiorazzi, M., Iqbal, J., Gesk, S., Siebert, R., De Jong, D., Jaffe, E.S., Wilson, W.H., Delabie, J., Ott, G., Dave, B.J., Sanger, W.G., Smith, L.M., Rimsza, L., Braziel, R.M., Müller-Hermelink, H.K., Campo, E., Gascoyne, R.D., Staudt, L.M., Chan, W.C. Blood (2005) [Pubmed]
  13. Assignment of the human cyclin D3 gene (CCND3) to chromosome 6p----q13. Motokura, T., Yi, H.F., Kronenberg, H.M., McBride, O.W., Arnold, A. Cytogenet. Cell Genet. (1992) [Pubmed]
  14. Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors". Bockstaele, L., Kooken, H., Libert, F., Paternot, S., Dumont, J.E., de Launoit, Y., Roger, P.P., Coulonval, K. Mol. Cell. Biol. (2006) [Pubmed]
  15. Detection of cyclin D1 (bcl-1, PRAD1) overexpression by a simple competitive reverse transcription-polymerase chain reaction assay in t(11;14)(q13;q32)-bearing B-cell malignancies and/or mantle cell lymphoma. Uchimaru, K., Taniguchi, T., Yoshikawa, M., Asano, S., Arnold, A., Fujita, T., Motokura, T. Blood (1997) [Pubmed]
  16. Identification of multiple cell cycle regulatory functions of p57Kip2 in human T lymphocytes. Li, G., Domenico, J., Lucas, J.J., Gelfand, E.W. J. Immunol. (2004) [Pubmed]
  17. Cyclin D3: requirement for G1/S transition and high abundance in quiescent tissues suggest a dual role in proliferation and differentiation. Bartkova, J., Lukas, J., Strauss, M., Bartek, J. Oncogene (1998) [Pubmed]
  18. Cyclin D3 expression in normal, reactive and neoplastic tissues. Doglioni, C., Chiarelli, C., Macrí, E., Dei Tos, A.P., Meggiolaro, E., Dalla Palma, P., Barbareschi, M. J. Pathol. (1998) [Pubmed]
  19. D-type cyclins in adult human testis and testicular cancer: relation to cell type, proliferation, differentiation, and malignancy. Bartkova, J., Rajpert-de Meyts, E., Skakkebaek, N.E., Bartek, J. J. Pathol. (1999) [Pubmed]
  20. Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line. Zhang, P., Zhang, Z., Zhou, X., Qiu, W., Chen, F., Chen, W. BMC Cancer (2006) [Pubmed]
  21. Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Mukhopadhyay, A., Banerjee, S., Stafford, L.J., Xia, C., Liu, M., Aggarwal, B.B. Oncogene (2002) [Pubmed]
  22. Differential Utilization of Cyclin D1 and Cyclin D3 in the Distinct Mitogenic Stimulations by Growth Factors and TSH of Human Thyrocytes in Primary Culture. Paternot, S., Dumont, J.E., Roger, P.P. Mol. Endocrinol. (2006) [Pubmed]
  23. Cyclin D3 immunoreactivity is an independent predictor of survival in laryngeal squamous cell carcinoma. Pruneri, G., Pignataro, L., Valentini, S., Fabris, S., Maisonneuve, P., Carboni, N., Pece, S., Capra, M., Del Curto, B., Neri, A., Viale, G. Clin. Cancer Res. (2005) [Pubmed]
  24. Ketoconazole induces G0/G1 arrest in human colorectal and hepatocellular carcinoma cell lines. Chen, R.J., Lee, W.S., Liang, Y.C., Lin, J.K., Wang, Y.J., Lin, C.H., Hsieh, J.Y., Chaing, C.C., Ho, Y.S. Toxicol. Appl. Pharmacol. (2000) [Pubmed]
  25. Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3. Shen, X., Yang, Y., Liu, W., Sun, M., Jiang, J., Zong, H., Gu, J. FEBS Lett. (2004) [Pubmed]
  26. Cyclin D3 interacts with vitamin D receptor and regulates its transcription activity. Jian, Y., Yan, J., Wang, H., Chen, C., Sun, M., Jiang, J., Lu, J., Yang, Y., Gu, J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  27. Regulation of the cyclin D3 promoter by E2F1. Ma, Y., Yuan, J., Huang, M., Jove, R., Cress, W.D. J. Biol. Chem. (2003) [Pubmed]
  28. Modulation of the p27kip1 cyclin-dependent kinase inhibitor expression during IL-4-mediated human B cell activation. Blanchard, D.A., Affredou, M.T., Vazquez, A. J. Immunol. (1997) [Pubmed]
  29. Nuclear phospholipase C beta1, regulation of the cell cycle and progression of acute myeloid leukemia. Cocco, L., Manzoli, L., Palka, G., Martelli, A.M. Adv. Enzyme Regul. (2005) [Pubmed]
  30. Cell cycle regulatory proteins and apoptosis in B-cell chronic lymphocytic leukemia. Wolowiec, D., Ciszak, L., Kosmaczewska, A., Bocko, D., Teodorowska, R., Frydecka, I., Kuliczkowski, K. Haematologica (2001) [Pubmed]
  31. Cyclin D3 expression in non-Hodgkin lymphoma. Correlation with other cell cycle regulators and clinical features. Møller, M.B., Nielsen, O., Pedersen, N.T. Am. J. Clin. Pathol. (2001) [Pubmed]
  32. SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway. Yuan, X., Wu, J., Shan, Y., Yao, Z., Dong, B., Chen, B., Zhao, Z., Wang, S., Chen, J., Cong, Y. Virology (2006) [Pubmed]
  33. ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells. Wei, Y., Jiang, J., Sun, M., Chen, X., Wang, H., Gu, J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  34. Varicella-zoster virus infection of human foreskin fibroblast cells results in atypical cyclin expression and cyclin-dependent kinase activity. Leisenfelder, S.A., Moffat, J.F. J. Virol. (2006) [Pubmed]
  35. Overexpression of G1-S cyclins and cyclin-dependent kinases during multistage human pancreatic duct cell carcinogenesis. Al-Aynati, M.M., Radulovich, N., Ho, J., Tsao, M.S. Clin. Cancer Res. (2004) [Pubmed]
  36. Expression of cyclin D3 and cyclin E and identification of distinct clusters of proliferation and apoptosis in diffuse large B-cell lymphomas. Bai, M., Tsanou, E., Agnantis, N.J., Chaidos, A., Dimou, D., Skyrlas, A., Dimou, S., Vlychou, M., Galani, V., Kanavaros, P. Histol. Histopathol. (2003) [Pubmed]
  37. Molecular control of the cell cycle in cancer: biological and clinical aspects. Møller, M.B. Danish medical bulletin. (2003) [Pubmed]
  38. CyclinD1/CyclinD3 ratio by real-time PCR improves specificity for the diagnosis of mantle cell lymphoma. Jones, C.D., Darnell, K.H., Warnke, R.A., Zehnder, J.L. The Journal of molecular diagnostics : JMD. (2004) [Pubmed]
  39. Phenotype-related differences in the expression of D-type cyclins in human B cell-derived lines. Pokrovskaja, K., Ehlin-Henriksson, B., Bartkova, J., Bartek, J., Scuderi, R., Szekely, L., Wiman, K.G., Klein, G. Cell Growth Differ. (1996) [Pubmed]
WikiGenes - Universities