RARs and RXRs: evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo.

Date

1993-06
Language
American English

Embargo Lift Date

Department

Committee Members

Degree

Degree Year

Department

Grantor

Journal Title

Journal ISSN

Volume Title

Found At

EMBO Press

Abstract

We have previously reported that the AB regions of retinoic acid receptors (RARs and RXRs) contain a transcriptional activation function capable of modulating the activity of the ligand-dependent activation function present in the C-terminal DE regions of these receptors. However, we could not demonstrate that these AB regions possess an autonomous activation function similar to the AF-1s found in the AB regions of steroid hormone receptors. Using the mouse CRBPII promoter as a reporter gene, we now report that the AB regions of RAR alpha, beta and gamma, as well as those of RXR alpha and gamma, contain an autonomous, ligand-independent activation function, AF-1, which can efficiently synergize with AF-2s. Moreover, AF-1s account for the ligand-independent, constitutive activation of transcription by RXR alpha and gamma. We also show that RARs and RXRs preferentially heterodimerize in solution in cultured cells in vivo, through the dimerization interface present in their E region, irrespective of the presence of all-trans or 9-cis retinoic acid. Furthermore, our results indicate that homodimeric interactions are not observed in cultured cells in vivo under conditions where heterodimeric interactions readily occur, which is in agreement with previous observations showing the preferential binding of RAR-RXR heterodimers to RA response elements in vitro.

Description

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC413465/
Keywords

item.page.description.tableofcontents

item.page.relation.haspart

Cite As

Nagpal, S., Friant, S., Nakshatri, H., & Chambon, P. (1993). RARs and RXRs: evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo. The EMBO Journal, 12(6), 2349–2360.

ISSN

0261-4189

Publisher

Series/Report

Sponsorship

Major

Extent

Identifier

Relation

Journal

Rights

Source

Alternative Title

Type

Article

Number

Volume

Conference Dates

Conference Host

Conference Location

Conference Name

Conference Panel

Conference Secretariat Location

Version

Full Text Available at

This item is under embargo {{howLong}}