E1A functions as a coactivator of retinoic acid-dependent retinoic acid receptor-beta 2 promoter activation.

Abstract

The retinoic acid (RA) receptor (RAR) beta 2 promoter is strongly activated by RA in embryonal carcinoma (EC) cells. We examined this activation in the P19 EC-derived END-2 cell line and in E1A-expressing counterparts and found strong RA-dependent RAR beta 2 promoter activation in the E1A-expressing cells, which was not observed in the parental cell line, indicating a possible role for E1A in RAR beta 2 activation. In transient transfection assays, E1A functioned as a coactivator of RA-dependent RAR beta 2 promoter activation and, moreover, was able to restore this activation in cells lacking RAR beta 2 activation. By deletion analysis, two regions in the RAR beta 2 promoter were identified that mediate the stimulatory effect of E1A: the RA response element and TATA box-containing region and a more up-stream region between -180 and -63, in which a cAMP response element-related motif was identified as a target element for E1A. In addition, determination of endogenous E1A-like activity by measuring E2A promoter activity in transient transfection assays in EC and differentiated cells revealed a correlation between RA-dependent RAR beta 2 promoter activation and the presence of this activity, suggesting an important role for the cellular equivalent of E1A in regulation of the RAR beta 2 promoter.

• Authors: F A Kruyt, G E Folkers, A J Walhout, B J van der Leede, P T van der Saag
• Journal: Molecular endocrinology (Baltimore, Md.) (Mol Endocrinol) Vol. 7 Issue 4 Pg. 604-15 (Apr 1993) ISSN: 0888-8809 [Print] United States
• PMID: 8389000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenovirus E1A Proteins
• Carrier Proteins
• Cyclic AMP Response Element-Binding Protein
• Receptors, Retinoic Acid
• Recombinant Fusion Proteins
• Tretinoin
• Chloramphenicol O-Acetyltransferase

Topics

• Adenovirus E1A Proteins (genetics, pharmacology, physiology)
• Animals
• Base Sequence
• Binding Sites
• Carrier Proteins (genetics)
• Chloramphenicol O-Acetyltransferase (genetics)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Embryonal Carcinoma Stem Cells
• Gene Expression
• Mice
• Molecular Sequence Data
• Neoplastic Stem Cells
• Promoter Regions, Genetic
• Receptors, Retinoic Acid
• Recombinant Fusion Proteins
• Transfection
• Tretinoin (pharmacology)
• Tumor Cells, Cultured