PTOV1 antagonizes MED25 in RAR transcriptional activation.

Abstract

Retinoic acid (RA) plays a role in cancer therapy. However, its long-term treatment is hindered by the acquired resistance which is not fully understood. Our previous study indicated that the transcriptional activity of RA receptor (RAR) is enhanced by association of MED25 with CREB-binding protein (CBP) through the PTOV domain, which is also present in prostate tumor over-expressed protein 1 (PTOV1). Here, we show that MED25 and PTOV1 reciprocally regulate RAR transcriptional activity through competitive bindings to CBP and opposite regulation of CBP recruitment to the RA-responsive gene promoter. Finally, we demonstrate that MED25 and PTOV1 differentially modulate RA sensitivity in cancer cells depending on their expression levels, suggesting a potential molecular mechanism underlying RA resistance which frequently emerges during cancer treatments.

• Authors: Hye-Sook Youn, Ui-Hyun Park, Eun-Joo Kim, Soo-Jong Um
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 404 Issue 1 Pg. 239-44 (Jan 07 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21110951 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Chromatin
• MED25 protein, human
• Mediator Complex
• Neoplasm Proteins
• PTOV1 protein, human
• Receptors, Retinoic Acid
• Tretinoin
• CREB-Binding Protein

Topics

• Antineoplastic Agents (pharmacology)
• Biomarkers, Tumor (metabolism)
• CREB-Binding Protein (metabolism)
• Cell Line
• Chromatin (metabolism)
• Chromatin Immunoprecipitation
• Drug Resistance, Neoplasm (genetics)
• Humans
• Mediator Complex (antagonists & inhibitors, metabolism)
• Neoplasm Proteins (metabolism)
• Neoplasms (genetics, metabolism)
• Receptors, Retinoic Acid (metabolism)
• Transcriptional Activation
• Tretinoin (pharmacology)