DOI: 10.1073/pnas.90.7.2989. Functional inhibition of retinoic acid response by dominant negative retinoic acid receptor mutants.

Functional inhibition of retinoic acid response by dominant negative retinoic acid receptor mutants.

10.1073/pnas.90.7.2989

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The diverse effects of retinoids on the development, growth, and homeostasis of vertebrate organisms are mediated in part by three distinct isoforms of retinoic acid receptors (RARs). These proteins, which are structurally and functionally closely related to thyroid hormone receptors and the oncogene product v-ErbA, regulate patterns of gene expression in target tissues. One approach to study the distinct effects of retinoic acid in cells is to subvert this activity of endogenous receptors by expression of dominant negative receptor derivatives. We demonstrate here that RAR alpha, RAR beta, and RAR gamma can be converted into potent negative transcriptional regulators that block wild-type RAR function. Furthermore, these mutant RARs, but not the wild-type receptors, actively repress the basal transcription level of target promoters. When expressed in transgenic mice, the most potent of these inhibitory receptor mutants is apparently able to disturb developmental processes by inducing a cleft palate in transgenic offspring.

Bibliography

Damm, K., Heyman, R. A., Umesono, K., & Evans, R. M. (1993). Functional inhibition of retinoic acid response by dominant negative retinoic acid receptor mutants. Proceedings of the National Academy of Sciences, 90(7), 2989â2993.

Authors 4

K Damm (first)
R A Heyman (additional)
K Umesono (additional)
R M Evans (additional)

References 0 Referenced 146

None

Dates

Type	When
Created	19 years, 3 months ago (May 31, 2006, 8:42 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 1:49 p.m.)
Indexed	11 months, 2 weeks ago (Sept. 13, 2024, 12:42 p.m.)
Issued	32 years, 5 months ago (April 1, 1993)
Published	32 years, 5 months ago (April 1, 1993)
Published Online	32 years, 5 months ago (April 1, 1993)
Published Print	32 years, 5 months ago (April 1, 1993)

Funders 0

None

BibTeX

@article{Damm_1993, title={Functional inhibition of retinoic acid response by dominant negative retinoic acid receptor mutants.}, volume={90}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.90.7.2989}, DOI={10.1073/pnas.90.7.2989}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Damm, K and Heyman, R A and Umesono, K and Evans, R M}, year={1993}, month=apr, pages={2989–2993} }

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