Zusammenfassung
AP-2 transcription factors execute important functions during embryonic development and malignant transformation. Recently, we have isolated a transcriptional repressor of AP-2 alpha expression, the novel Kruppel-related zinc finger protein AP-2rep (KIf12). Here, we show that repression of AP-2 alpha transcription by AP-2rep is dependent on an N-terminal PVDLS motif that interacts specifically ...
Zusammenfassung
AP-2 transcription factors execute important functions during embryonic development and malignant transformation. Recently, we have isolated a transcriptional repressor of AP-2 alpha expression, the novel Kruppel-related zinc finger protein AP-2rep (KIf12). Here, we show that repression of AP-2 alpha transcription by AP-2rep is dependent on an N-terminal PVDLS motif that interacts specifically with the corepressor CtBP1 both in vivo and in vitro. This interaction motif was previously identified in the C-terminal region of the adenoviral oncoprotein EIA. Infection of both HeLa and PA-1. cells with adenovirus type 5 strongly induced AP-2 alpha mRNA. Consistently, EIA was necessary and sufficient to mediate up-regulation of AP-2 alpha. Transiently transfected wild-type EIA protein activated an AP-2rep sensitive cis-regulatory element of the AP-2 alpha promoter, but E1A protein harboring a mutation in the PVDLS motif failed to activate. In summary, we conclude that the adenoviral oncoprotein EIA activates transcription from the endogenous AP-2 alpha gene, an effect that involves transcriptional derepression of the AP-2 alpha promoter by interaction of E1A with the AP-2rep corepressor CtBP1.
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