Affiliation:
1. Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
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 AP-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 AP-2B exerts its inhibitory function, we purified bacterially expressed AP-2A and AP-2B proteins. While bacterial AP-2B does not bind an AP-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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference60 articles.
1. Human teratocarcinomas;Andrews P.;Biochim. Biophys. Acta,1988
2. The jun proto-oncogene is positively autoregulated by its product, jun/ AP-1;Angel P.;Cell,1988
3. Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wtl gene transcript;Bickmore W. A.;Science,1992
4. Alteration of homeobox gene expression by N-ras transformation of PA-1 human teratocarcinoma cells;Buettner R.;Mol. Cell. Biol.,1991
5. Susceptibility to ras oncogene transformation is coregulated with signal transduction through growth factor receptors;Chiao P. J.;Oncogene,1991
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献