BUETTNER, R and KANNAN, P and IMHOF, A and BAUER, R and YIM, SO and GLOCKSHUBER, R and VANDYKE, MW and TAINSKY, MA (1993) AN ALTERNATIVELY SPLICED MESSENGER-RNA FROM THE AP-2 GENE ENCODES A NEGATIVE REGULATOR OF TRANSCRIPTIONAL ACTIVATION BY AP-2. MOLECULAR AND CELLULAR BIOLOGY, 13 (7). pp. 4174-4185. ISSN 0270-7306,
Full text not available from this repository.Abstract
AP-2 is a retinoic acid-inducible and developmentally regulated activator of transcription. We have cloned an alternative AP-2 transcript (AP-2B) from the human teratocarcinoma cell line PA-1, which encodes a protein differing in the C terminus from the previously isolated AP-2 protein (AP-2A). This protein contains the activation domain of AP-2 and part of the DNA binding domain but lacks the dimerization domain which is necessary for DNA binding. Analysis of overlapping genomic clones spanning the entire AP-2 gene proves that AP-2A and AP-2B transcripts are alternatively spliced from the same gene. Both transient and stable transfection experiments show that A.P-2B inhibits AP-2 transactivator function, as measured by an AP-2-responsive chloramphenicol acetyltransferase reporter plasmid. Furthermore, constitutive AP-2B expression in PA-1 cells causes a retinoic acid-resistant phenotype, anchorage-independent growth in soft agar, and tumorigenicity in nude mice, in a fashion similar to transformation of these cells by oncogenes. To determine the mechanism by which A.P-2B exerts its inhibitory function, we purified bacterially expressed AP-2A and AP-2B proteins. While bacterial AP-2B does not bind an A.P-2 consensus site, it strongly inhibits binding of the endogenous AP-2 present in PA-1 cell nuclear extracts. However, DNA sequence-specific binding of bacterially expressed AP-2A cannot be inhibited by bacterially expressed AP-2B. Therefore, inhibition of AP-2 activity by the protein AP-2B may require an additional factor or modification supplied by nuclear extracts.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DNA-BINDING; TERATOCARCINOMA CELLS; SIGNAL-TRANSDUCTION; INDUCIBLE ENHANCER; CARCINOMA-CELLS; RETINOIC ACID; RAS ONCOGENE; PROTEIN; EXPRESSION; TRANSFORMATION; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/53904 |
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