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Gene Review

Ccnd1  -  cyclin D1

Rattus norvegicus

Synonyms: G1/S-specific cyclin-D1
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Disease relevance of Ccnd1


High impact information on Ccnd1


Chemical compound and disease context of Ccnd1


Biological context of Ccnd1


Anatomical context of Ccnd1


Associations of Ccnd1 with chemical compounds


Physical interactions of Ccnd1


Regulatory relationships of Ccnd1

  • Thus, ET-1 induced cyclin D1 expression and stimulated CDK4 activity and cell cycle progression via the A-type receptor in rat mesangial cells [18].
  • In exponentially growing cultures, TGF-beta 1 blocked DNA synthesis and suppressed cyclin D1 mRNA and protein expression, whereas the levels of cyclins D2, D3 and Cdk4 remained relatively unchanged [17].
  • Under these conditions, CDK2 and CDK4 protein expression remained unchanged compared with proliferating cells, but expression of cyclin D1 and p27(KIP1) was down-regulated and cyclin E accumulated in the inactive form [25].
  • This shape-dependent block in cell proliferation correlated with a failure to increase cyclin D1 protein level and to down-regulate the cell cycle inhibitor p27 [26].
  • Cyclin D1 was up-regulated in the mid-G1 phase (4-6 h) while cyclin D3 expression emerged only in late G1 (9-12 h) [27].

Other interactions of Ccnd1

  • The data suggest that the NO-PKG pathway inhibits AGE-induced proliferation by suppressing activation of JAK2-STAT5 and cyclin D1/cdk4 and induction of p21Waf1/Cip1 [13].
  • Activated-Akt can activate downstream signal protein [p70(S6 K), nuclear factor (NF)-kappaB, and extracellular signal regulated kinase (ERK)], increasing the cyclin D1 level and suppressing the transcription of p27(Kip1) to enable cell cycle entry [28].
  • These results indicate that cyclin D1 may be involved in the regeneration of hepatocytes rather than hepatocarcinogenesis, while Cdk4 but not Cdk6 may play an important role in the development of HCC [4].
  • By contrast, significantly stronger beta-catenin and Cyclin D1 mRNA expressions and protein levels were found in CsA-treated rats than controls by RT-PCR and immunohistochemistry at week 4, whereas PCNA production was stronger at both times [29].
  • CONCLUSIONS: Daily administration of low dose TA makes cell cycle open and G1 progress, possibly due to cyclin D1, CDK4 and CDK 6, their transporter p21(CIP1), and inactive p16(INK4a), which occur at quiescent hepatocytes, not stem cells [30].

Analytical, diagnostic and therapeutic context of Ccnd1


  1. Hepatocellular carcinoma cell cycle: study of Long-Evans cinnamon rats. Masaki, T., Shiratori, Y., Rengifo, W., Igarashi, K., Matsumoto, K., Nishioka, M., Hatanaka, Y., Omata, M. Hepatology (2000) [Pubmed]
  2. Cyclooxygenase-2 induction and transforming growth factor beta growth inhibition in rat intestinal epithelial cells. Sheng, H., Shao, J., Hooton, E.B., Tsujii, M., DuBois, R.N., Beauchamp, R.D. Cell Growth Differ. (1997) [Pubmed]
  3. Cyclooxygenase-2 activity contributes to neuronal expression of cyclin D1 after anoxia/ischemia in vitro and in vivo. Wu Chen, R., Zhang, Y., Rose, M.E., Graham, S.H. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  4. Expression of G1 phase-related cell cycle molecules in naturally developing hepatocellular carcinoma of Long-Evans Cinnamon rats. Kita, Y., Masaki, T., Funakoshi, F., Yoshida, S., Tanaka, M., Kurokohchi, K., Uchida, N., Watanabe, S., Matsumoto, K., Kuriyama, S. Int. J. Oncol. (2004) [Pubmed]
  5. Tumor-selective transgene expression in vivo mediated by an E2F-responsive adenoviral vector. Parr, M.J., Manome, Y., Tanaka, T., Wen, P., Kufe, D.W., Kaelin, W.G., Fine, H.A. Nat. Med. (1997) [Pubmed]
  6. Retinoic acid uses divergent mechanisms to activate or suppress mitogenesis in rat aortic smooth muscle cells. Chen, S., Gardner, D.G. J. Clin. Invest. (1998) [Pubmed]
  7. Cisplatin-induced apoptosis in rat dorsal root ganglion neurons is associated with attempted entry into the cell cycle. Gill, J.S., Windebank, A.J. J. Clin. Invest. (1998) [Pubmed]
  8. Analysis of cell cycle-related gene expression in postmitotic neurons: selective induction of Cyclin D1 during programmed cell death. Freeman, R.S., Estus, S., Johnson, E.M. Neuron (1994) [Pubmed]
  9. NO sensitizes rat hepatocytes to proliferation by modifying S-adenosylmethionine levels. García-Trevijano, E.R., Martínez-Chantar, M.L., Latasa, M.U., Mato, J.M., Avila, M.A. Gastroenterology (2002) [Pubmed]
  10. Aberrant expression of p27(Kip1) is associated with malignant transformation of the rat urinary bladder epithelium. Ogawa, K., Kimoto, N., Asamoto, M., Nakanishi, M., Takahashi, S., Shirai, T. Carcinogenesis (2000) [Pubmed]
  11. Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin. Wali, R.K., Khare, S., Tretiakova, M., Cohen, G., Nguyen, L., Hart, J., Wang, J., Wen, M., Ramaswamy, A., Joseph, L., Sitrin, M., Brasitus, T., Bissonnette, M. Cancer Epidemiol. Biomarkers Prev. (2002) [Pubmed]
  12. HMG-CoA reductase inhibitor fluvastatin prevents angiotensin II-induced cardiac hypertrophy via Rho kinase and inhibition of cyclin D1. Morikawa-Futamatsu, K., Adachi, S., Maejima, Y., Tamamori-Adachi, M., Suzuki, J., Kitajima, S., Ito, H., Isobe, M. Life Sci. (2006) [Pubmed]
  13. Effect of nitric oxide-cGMP-dependent protein kinase activation on advanced glycation end-product-induced proliferation in renal fibroblasts. Huang, J.S., Chuang, L.Y., Guh, J.Y., Chen, C.J., Yang, Y.L., Chiang, T.A., Hung, M.Y., Liao, T.N. J. Am. Soc. Nephrol. (2005) [Pubmed]
  14. Regulation of the hepatocyte cell cycle by type I collagen matrix: role of cyclin D1. Hansen, L.K., Albrecht, J.H. J. Cell. Sci. (1999) [Pubmed]
  15. Differential expression patterns of Wnt and beta-catenin/TCF target genes in the uterus of immature female rats exposed to 17alpha-ethynyl estradiol. Katayama, S., Ashizawa, K., Fukuhara, T., Hiroyasu, M., Tsuzuki, Y., Tatemoto, H., Nakada, T., Nagai, K. Toxicol. Sci. (2006) [Pubmed]
  16. Potassium-induced apoptosis in rat cerebellar granule cells involves cell-cycle blockade at the G1/S transition. Martín-Romero, F.J., Santiago-Josefat, B., Correa-Bordes, J., Gutierrez-Merino, C., Fernandez-Salguero, P. J. Mol. Neurosci. (2000) [Pubmed]
  17. 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]
  18. Cyclin D1, p16, and retinoblastoma gene regulate mitogenic signaling of endothelin in rat mesangial cells. Terada, Y., Inoshita, S., Nakashima, O., Yamada, T., Tamamori, M., Ito, H., Sasaki, S., Marumo, F. Kidney Int. (1998) [Pubmed]
  19. Transit of normal rat uterine stromal cells through G1 phase of the cell cycle requires progesterone-growth factor interactions. Jones, S.R., Kimler, B.F., Justice, W.M., Rider, V. Endocrinology (2000) [Pubmed]
  20. 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]
  21. Intestinal cell cycle regulations. Interactions of cyclin D1, Cdk4, and p21Cip1. Beauchamp, R.D., Sheng, H.M., Shao, J.Y., Thompson, E.A., Ko, T.C. Ann. Surg. (1996) [Pubmed]
  22. Expression and function of Ets-1 during experimental acute renal failure in rats. Tanaka, H., Terada, Y., Kobayashi, T., Okado, T., Inoshita, S., Kuwahara, M., Seth, A., Sato, Y., Sasaki, S. J. Am. Soc. Nephrol. (2004) [Pubmed]
  23. Cyclosporine inhibits growth through the activating transcription factor/cAMP-responsive element-binding protein binding site in the cyclin D1 promoter. Schneider, G., Oswald, F., Wahl, C., Greten, F.R., Adler, G., Schmid, R.M. J. Biol. Chem. (2002) [Pubmed]
  24. Transcriptional regulation of rat cyclin D1 gene by CpG methylation status in promoter region. Kitazawa, S., Kitazawa, R., Maeda, S. J. Biol. Chem. (1999) [Pubmed]
  25. G1-arrested FaO cells re-enter the cell cycle upon stimulation with the rodent non-genotoxic hepatocarcinogen nafenopin. Chevalier, S., Roberts, R.A. Carcinogenesis (1999) [Pubmed]
  26. A p160ROCK-specific inhibitor, Y-27632, attenuates rat hepatic stellate cell growth. Iwamoto, H., Nakamuta, M., Tada, S., Sugimoto, R., Enjoji, M., Nawata, H. J. Hepatol. (2000) [Pubmed]
  27. 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]
  28. Blocking of Akt/NF-{kappa}B Signaling by Pentoxifylline Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation in Brown Norway Rat Airway Smooth Muscle Cells. Chiou, Y.L., Shieh, J.J., Lin, C.Y. Pediatr. Res. (2006) [Pubmed]
  29. Cyclosporin-induced downregulation of the expression of E-cadherin during proliferation of edentulous gingival epithelium in rats. Tu, H.P., Chen, Y.T., Shieh, Y.S., Chin, Y.T., Huang, R.Y., Yang, S.F., Gau, C.H., Fu, E. J. Periodontol. (2006) [Pubmed]
  30. Expression of G1 Cell Cycle Regulators in Rat Liver upon Repeated Exposure to Thioacetamide. Kim, K.T., Han, S.Y., Jeong, J.S. The Korean journal of hepatology (2007) [Pubmed]
  31. D-type cyclins and G1 progression during liver development in the rat. Boylan, J.M., Gruppuso, P.A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  32. Chronic iron overload stimulates hepatocyte proliferation and cyclin D1 expression in rodent liver. Brown, K.E., Mathahs, M.M., Broadhurst, K.A., Weydert, J. Translational research : the journal of laboratory and clinical medicine. (2006) [Pubmed]
  33. Liver regeneration is suppressed in small-for-size liver grafts after transplantation: involvement of c-Jun N-terminal kinase, cyclin D1, and defective energy supply. Zhong, Z., Schwabe, R.F., Kai, Y., He, L., Yang, L., Bunzendahl, H., Brenner, D.A., Lemasters, J.J. Transplantation (2006) [Pubmed]
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