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MINIREVIEW |
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC 20057-1468
Address all correspondence and requests for reprints to: Richard G. Pestell, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, 3970 Reservoir Road NW, Box 571468, Washington, DC 20057-1468. E-mail: pestell{at}georgetown.edu.
Abstract
Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein and promotes progression through the G1-S phase of the cell cycle. Amplification or overexpression of cyclin D1 plays pivotal roles in the development of a subset of human cancers including parathyroid adenoma, breast cancer, colon cancer, lymphoma, melanoma, and prostate cancer. Of the three D-type cyclins, each of which binds cyclin-dependent kinase (CDK), it is cyclin D1 overexpression that is predominantly associated with human tumorigenesis and cellular metastases. In recent years accumulating evidence suggests that in addition to its original description as a CDK-dependent regulator of the cell cycle, cyclin D1 also conveys cell cycle or CDK-independent functions. Cyclin D1 associates with, and regulates activity of, transcription factors, coactivators and corepressors that govern histone acetylation and chromatin remodeling proteins. The recent findings that cyclin D1 regulates cellular metabolism, fat cell differentiation and cellular migration have refocused attention on novel functions of cyclin D1 and their possible role in tumorigenesis. In this review, both the classic and novel functions of cyclin D1 are discussed with emphasis on the CDK-independent functions of cyclin D1.
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S. J. Zacharek, Y. Xiong, and S. D. Shumway Negative Regulation of TSC1-TSC2 by Mammalian D-Type Cyclins Cancer Res., December 15, 2005; 65(24): 11354 - 11360. [Abstract] [Full Text] [PDF]
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D. Xiao, D. Chinnappan, R. Pestell, C. Albanese, and H. C. Weber Bombesin Regulates Cyclin D1 Expression through the Early Growth Response Protein Egr-1 in Prostate Cancer Cells Cancer Res., November 1, 2005; 65(21): 9934 - 9942. [Abstract] [Full Text] [PDF]
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 M. Thangaraju, M. Rudelius, B. Bierie, M. Raffeld, S. Sharan, L. Hennighausen, A-M. Huang, and E. Sterneck C/EBP{delta} is a crucial regulator of pro-apoptotic gene expression during mammary gland involution Development, November 1, 2005; 132(21): 4675 - 4685. [Abstract] [Full Text] [PDF]
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