We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A central domain of cyclin D1 mediates nuclear receptor corepressor activity.

Oncogene | Jan 13, 2005

Regulation of nuclear receptor activity is the focus of numerous ongoing studies to develop novel therapies for the treatment of hormone-related cancer. Although cyclin D1 functions to control the activity of several nuclear receptors, the region(s) of the protein responsible for such transcriptional comodulation remain poorly defined. Herein, we map the region of cyclin D1 required for binding and repression of the androgen receptor (AR) to a central, exclusively alpha-helical domain. Deletion of this domain disrupted AR binding and corepressor activity. Further investigations showed that this domain is sufficient for AR interaction and possesses the ability to bind histone deacetylase 3. Strikingly, overexpression of this repressor region attenuates cell cycle progression in prostatic adenocarcinoma cells. The requirement of this domain for nuclear receptor repression was conserved with respect to thyroid hormone receptor beta-1, whereas cyclin D1 activation of the estrogen receptor occurred independently of the central region. Together, these data identify a minimal repression module within cyclin D1 and demonstrate that the coactivator and corepressor functions of cyclin D1 are distinct. In addition, our data suggest that properties of the cyclin D1 central domain could be exploited to develop novel prostate cancer therapeutics.

Pubmed ID: 15558026 RIS Download

Mesh terms: Amino Acid Sequence | Animals | COS Cells | Cercopithecus aethiops | Cyclin D1 | Flow Cytometry | Genes, Reporter | Humans | Male | Models, Molecular | Molecular Sequence Data | Plasmids | Prostatic Neoplasms | Protein Conformation | Receptors, Androgen | Sequence Deletion | Transfection

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA93237
  • Agency: NICHD NIH HHS, Id: HDO7200-15
  • Agency: NIEHS NIH HHS, Id: P30-ES06096
  • Agency: NCI NIH HHS, Id: R01 CA099996

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.