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PMID: 7565739 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Adenovirus E1A functions as a cofactor for retinoic acid receptor beta (RAR beta) through direct interaction with RAR beta.

Molecular and cellular biology ·Vol. 15 ·No. 11 ·1995-11-00 ·Pages 5868-78

Folkers GE, van der Saag PT

Abstract

Transcription regulation by DNA-bound activators is thought to be mediated by a direct interaction between these proteins and TATA-binding protein (TBP), TFIIB, or TBP-associated factors, although occasionally cofactors or adapters are required. For ligand-induced activation by the retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer, the RAR beta 2 promoter is dependent on the presence of E1A or E1A-like activity, since this promoter is activated by retinoic acid only in cells expressing such proteins. The mechanism underlying this E1A requirement is largely unknown. We now show that direct interaction between RAR and E1A is a requirement for retinoic acid-induced RAR beta 2 activation. The activity of the hormone-dependent activation function 2 (AF-2) of RAR beta is upregulated by E1A, and an interaction between this region and E1A was observed, but not with AF-1 or AF-2 of RXR alpha. This interaction is dependent on conserved region III (CRIII), the 13S mRNA-specific region of E1A. Deletion analysis within this region indicated that the complete CRIII is needed for activation. The putative zinc finger region is crucial, probably as a consequence of interaction with TBP. Furthermore, the region surrounding amino acid 178, partially overlapping with the TBP binding region, is involved in both binding to and activation by AF-2. We propose that E1A functions as a cofactor by interacting with both TBP and RAR, thereby stabilizing the preinitiation complex.

MeSH Terms
Adenovirus E1A Proteins/metabolism Amino Acid Sequence Animals Binding Sites Cell Differentiation Cells, Cultured Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Mice Molecular Sequence Data Promoter Regions, Genetic Protein Binding RNA, Messenger/genetics Receptors, Retinoic Acid/metabolism Transcription, Genetic Tretinoin/metabolism Tumor Cells, Cultured Zinc Fingers
Chemicals
Adenovirus E1A Proteins RNA, Messenger Receptors, Retinoic Acid retinoic acid receptor beta Tretinoin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Folkers G E
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands.
van der Saag P T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.11.5868
Published
1995-11-00
Pages
5868-78
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230838
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.15.11.5868 PMC Full Text View journal details
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