The Proliferating Cell Nuclear Antigen Regulates Retinoic Acid Receptor Transcriptional Activity Through Direct Protein-protein Interaction

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2005 Aug 2

PMID 16055921

Citations 10

Authors

Perrine J Martin

Virginie Lardeux

Philippe Lefebvre

Affiliations

Soon will be listed here.

Abstract

Retinoic acid receptors (RARs) interact, in a ligand-dependent fashion, with many coregulators that participate in a wide spectrum of biological responses, ranging from embryonic development to cellular growth control. The transactivating function of these ligand-inducible transcription factors reside mainly, but not exclusively, in their ligand-binding domain (AF2), which recruits or dismiss coregulators in a ligand-dependent fashion. However, little is known about AF2-independent function(s) of RARs. We have isolated the proliferating cell nuclear antigen (PCNA) as a repressor of RAR transcriptional activity, able to interact with an AF2-crippled RAR. The N-terminus of PCNA interacts directly with the DNA-binding domain of RAR, and PCNA is recruited to a retinoid-regulated promoter in intact cells. This interaction affects the transcriptional response to retinoic acid in a promoter-specific manner, conferring an unanticipated role to PCNA in transcriptional regulation. Our findings also suggest a role for RAR as a factor coordinating DNA transcription and repair.

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