PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator Journal Article
| Authors: | Pavri, R.; Lewis, B.; Kim, T. K.; Dilworth, F. J.; Erdjument-Bromage, H.; Tempst, P.; De Murcia, G.; Evans, R.; Chambon, P.; Reinberg, D. |
| Article Title: | PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator |
| Abstract: | We show that PARP-1 is indispensable to retinoic acid receptor (RAR)-mediated transcription from the RARβ2 promoter in a highly purified, reconstituted transcription system and that RA-inducible expression of all RARβ isoforms is abrogated in PARP-1-/- cells in vivo. Importantly, PARP-1 activity was independent of its catalytic domain. PARP-1 directly interacts with RAR and Mediator. Chromatin immunoprecipitation experiments confirmed the presence of PARP-1 and Mediator on RAR-responsive promoters in vivo. Importantly, Mediator was inactive (Cdk8+) under basal conditions but was activated (Cdk8-) upon induction. However, in PARP-1-/- cells, Mediator was retained in its inactive state (Cdk8+) upon induction consistent with the absence of gene expression. PARP-1 became dispensable for ligand-dependent transcription in a chromatin reconstituted transcription assay when Mediator was devoid of the Cdk8 module (CRSP). PARP-1 appears to function as a specificity factor regulating the RA-induced switch of Mediator from the inactive (Cdk8+) to the active (Cdk8-) state in RAR-dependent transcription. Copyright ©2005 by Elsevier Inc. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; promoter region; gene deletion; nonhuman; protein function; animal cell; mouse; animals; gene expression; cyclin dependent kinase 8; protein protein interaction; cell line; genetic transcription; transcription, genetic; enzyme activity; hela cells; transfection; reverse transcriptase polymerase chain reaction; chromatin; recombinant proteins; immunoprecipitation; dimerization; cell nucleus; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; isoprotein; enzyme active site; retinoic acid receptor; poly(adp-ribose) polymerases; mediator; retinoic acid receptor beta; receptors, retinoic acid; polyadenosine diphosphate ribose polymerase 1 |
| Journal Title: | Molecular Cell |
| Volume: | 18 |
| Issue: | 1 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2005-04-01 |
| Start Page: | 83 |
| End Page: | 96 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2005.02.034 |
| PUBMED: | 15808511 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 106" - "Export Date: 24 October 2012" - "CODEN: MOCEF" - "Source: Scopus" |
