| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 1, 2004
Accepted on November 3, 2004
Department of Cell Biology, and Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521; Laboratories of Reproductive Biology, and the Department of Pediatrics and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7500
* To whom correspondence should be addressed. E-mail: Karen.Knudsen{at}uc.edu.
The androgen receptor (AR) is a member of the nuclear receptor superfamily whose activity is critical for the development and progression of prostate cancer. We and others have previously demonstrated that cyclin D1 is a potent co-repressor of the AR. Although cyclin D1 is suspected to recruit histone deacetylases to the AR complex, previous studies have demonstrated that this activity alone is insufficient for cyclin D1 function. Here, we uncover a novel, secondary means of cyclin D1 mediated repression, through modulation of AR amino-carboxy terminal interactions. We show that cyclin D1 predominantly binds the amino terminal domain (NTD) of the AR, dependent on the AR 23FxxLF27 motif. Through this motif, cyclin D1 abrogates the ability of the AR NTD to interact with the carboxy terminus. Secondary NTD sites capable of fostering interaction with the C-terminus were refractory to cyclin D1 action, indicating that the ability of cyclin D1 to modulate AR amino-carboxy terminal interactions is specific to 23FxxLF27. Deletion of the N-terminal cyclin D1 binding site severely compromised AR activity (due to loss of FxxLF), but unmasked a repressor action through interaction with the AR C-terminus and an unexpected role for cyclin D1 in activating AF-2. In summary, these data reveal novel, unexpected mechanisms of cyclin D1 activity, and demonstrate that this function of cyclin D1 is critical for AR modulation.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  H. V. Heemers and D. J. Tindall Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex Endocr. Rev., December 1, 2007; 28(7): 778 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zong, Y. Chi, Y. Wang, Y. Yang, L. Zhang, H. Chen, J. Jiang, Z. Li, Y. Hong, H. Wang, et al. Cyclin D3/CDK11p58 Complex Is Involved in the Repression of Androgen Receptor Mol. Cell. Biol., October 15, 2007; 27(20): 7125 - 7142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Huang, B. Jiao, C. K. Fung, Y. Zhang, W. K K Ho, C. B. Chan, H. Lin, D. Wang, and C. H K Cheng The presence of two distinct prolactin receptors in seabream with different tissue distribution patterns, signal transduction pathways and regulation of gene expression by steroid hormones J. Endocrinol., August 1, 2007; 194(2): 373 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J Burd, L. M Morey, and K. E Knudsen Androgen receptor corepressors and prostate cancer Endocr. Relat. Cancer, December 1, 2006; 13(4): 979 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Carascossa, J. Gobinet, V. Georget, A. Lucas, E. Badia, A. Castet, R. White, J.-C. Nicolas, V. Cavailles, and S. Jalaguier Receptor-Interacting Protein 140 Is a Repressor of the Androgen Receptor Activity Mol. Endocrinol., July 1, 2006; 20(7): 1506 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Burd, C. E. Petre, L. M. Morey, Y. Wang, M. P. Revelo, C. A. Haiman, S. Lu, C. M. Fenoglio-Preiser, J. Li, E. S. Knudsen, et al. Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation PNAS, February 14, 2006; 103(7): 2190 - 2195. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
