Induction of AP-2alpha expression by adenoviral infection involves inactivation of the AP-2rep transcriptional corepressor CtBP1.
AP-2 transcription factors execute important functions during embryonic development and malignant transformation. Recently, we have isolated a transcriptional repressor of AP-2alpha expression, the novel Krüppel-related zinc finger protein AP-2rep (Klf12). Here, we show that repression of AP-2alpha 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 E1A. Infection of both HeLa and PA-1 cells with adenovirus type 5 strongly induced AP-2alpha mRNA. Consistently, E1A was necessary and sufficient to mediate up-regulation of AP-2alpha. Transiently transfected wild-type E1A protein activated an AP-2rep sensitive cis-regulatory element of the AP-2alpha promoter, but E1A protein harboring a mutation in the PVDLS motif failed to activate. In summary, we conclude that the adenoviral oncoprotein E1A activates transcription from the endogenous AP-2alpha gene, an effect that involves transcriptional derepression of the AP-2alpha promoter by interaction of E1A with the AP-2rep corepressor CtBP1.
Schuierer
M
M
Institute for Microbiology, University of Regensburg Medical School, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
Hilger-Eversheim
K
K
Dobner
T
T
Bosserhoff
A K
AK
Moser
M
M
Turner
J
J
Crossley
M
M
Buettner
R
R
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000429:Alcohol Oxidoreductases; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry*; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C493673:TFAP2A protein, human; C493668:Tfap2a protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein