E1A functions as a coactivator of retinoic acid-dependent retinoic acid receptor-beta 2 promoter activation.
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.
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
F A
FA
Kruyt
G E
GE
Folkers
A J
AJ
Walhout
B J
BJ
van der Leede
P T
PT
van der Saag
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054278:Embryonal Carcinoma Stem Cells; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D014212:Tretinoin; D015500:Chloramphenicol O-Acetyltransferase