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PMID: 1652063 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Retinoic acid-induced down-regulation of the interleukin-2 promoter via cis-regulatory sequences containing an octamer motif.

Molecular and cellular biology ·Vol. 11 ·No. 9 ·1991-09-00 ·Pages 4771-8

Felli MP, Vacca A, Meco D, Screpanti I, Farina AR, Maroder M, Martinotti S, Petrangeli E, Frati L, Gulino A

Abstract

Retinoic acid (RA) is known to influence the proliferation and differentiation of a wide variety of transformed and developing cells. We found that RA and the specific RA receptor (RAR) ligand Ch55 inhibited the phorbol ester and calcium ionophore-induced expression of the T-cell growth factor interleukin-2 (IL-2) gene. Expression of transiently transfected chloramphenicol acetyltransferase vectors containing the 5'-flanking region of the IL-2 gene was also inhibited by RA. RA-induced down-regulation of the IL-2 enhancer is mediated by RAR, since overexpression of transfected RARs increased RA sensitivity of the IL-2 promoter. Functional analysis of chloramphenicol acetyltransferase vectors containing either internal deletion mutants of the region from -317 to +47 bp of the IL-2 enhancer or multimerized cis-regulatory elements showed that the RA-responsive element in the IL-2 promoter mapped to sequences containing an octamer motif. RAR also inhibited the transcriptional activity of the octamer motif of the immunoglobulin heavy chain enhancer. In spite of the transcriptional inhibition of the IL-2 octamer motif, RA did not decrease the in vitro DNA-binding capability of octamer-1 protein. These results identify a regulatory pathway within the IL-2 promoter which involves the octamer motif and RAR.

MeSH Terms
Base Sequence Carrier Proteins/metabolism Cell Line DNA Down-Regulation Gene Expression Regulation Humans Interleukin-2/genetics Molecular Sequence Data Promoter Regions, Genetic RNA, Messenger/metabolism Receptors, Retinoic Acid Transcription, Genetic/drug effects Tretinoin/metabolism
Chemicals
Carrier Proteins Interleukin-2 RNA, Messenger Receptors, Retinoic Acid Tretinoin DNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Felli M P
Department of Experimental Medicine, University of L'Aquila, Italy.
Vacca A
Meco D
Screpanti I
Farina A R
Maroder M
Martinotti S
Petrangeli E
Frati L
Gulino A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.9.4771-4778.1991
Published
1991-09-00
Pages
4771-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361378
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.11.9.4771-4778.1991 PMC Full Text View journal details
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