Abstract |
Retinoids such as retinoic acid (RA) are potent anti-arthritic and anti-neoplastic agents. We investigated the mechanism by which RA inhibits induction of collagenase gene transcription by inflammatory mediators, tumor promoters, and proto-oncogenes. We found that the RA receptors (RARs) are potent inhibitors of AP-1 activity generated either by cJun homodimers or cJun/cFos heterodimers. In addition, both cJun and cFos can inhibit RAR activity. In vitro experiments suggested that this inhibition is due to an interaction between RAR and AP-1 proteins that results in mutual loss of DNA-binding activity. The RARs need not bind to the AP-1 site, neither does AP-1 bind to RA response elements. An understanding of this antagonism between the RAR and AP-1 might help to elucidate the anti-neoplastic and anti-arthritic effects of RA as well as its effects on cell differentiation and proliferation.
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Authors | H F Yang-Yen, X K Zhang, G Graupner, M Tzukerman, B Sakamoto, M Karin, M Pfahl |
Journal | The New biologist
(New Biol)
Vol. 3
Issue 12
Pg. 1206-19
(Dec 1991)
ISSN: 1043-4674 [Print] United States |
PMID | 1667479
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carrier Proteins
- Neoplasm Proteins
- Proto-Oncogene Proteins c-fos
- Proto-Oncogene Proteins c-jun
- Receptors, Retinoic Acid
- Tretinoin
- DNA
- Microbial Collagenase
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Topics |
- Base Sequence
- Carrier Proteins
(physiology)
- DNA
(metabolism)
- Gene Expression Regulation, Neoplastic
- Genetic Vectors
- HeLa Cells
- Humans
- Inflammation
(physiopathology)
- Microbial Collagenase
(biosynthesis)
- Molecular Sequence Data
- Neoplasm Proteins
(physiology)
- Neoplasms
(etiology)
- Plasmids
- Promoter Regions, Genetic
(drug effects)
- Proto-Oncogene Proteins c-fos
(physiology)
- Proto-Oncogene Proteins c-jun
(physiology)
- Receptors, Retinoic Acid
- Transcription, Genetic
(drug effects)
- Transfection
- Tretinoin
(pharmacology)
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