PTOV1 antagonizes MED25 in RAR transcriptional activation.
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.
Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea.
Hye-Sook
HS
Youn
Ui-Hyun
UH
Park
Eun-Joo
EJ
Kim
Soo-Jong
SJ
Um
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D056892:Mediator Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology*; D048868:Adaptor Proteins, Signal Transducing
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050882:CREB-Binding Protein; D002843:Chromatin; D056892:Mediator Complex; D009363:Neoplasm Proteins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; C483045:MED25 protein, human; C425183:PTOV1 protein, human; D048868:Adaptor Proteins, Signal Transducing