Analysis of a cAMP-responsive activator reveals a two-component mechanism for transcriptional induction via signal-dependent factors.
We have examined the mechanism by which the cAMP-responsive factor CREB stimulates target gene expression following its phosphorylation at Ser-133. Using an in vitro transcription assay, we found that two signals were required for target gene activation: a phospho(Ser-133)-dependent interaction of CREB with RNA polymerase II via the coactivator CBP and a glutamine-rich domain interaction with TFIID via hTAF(II)130. The adenovirus E1A oncoprotein was found to inhibit phospho(Ser-133) CREB activity by binding to CBP and specifically blocking recruitment of RNA Pol II to the promoter. Our results suggest that the recruitment of CBP-RNA Pol II complexes per se is not sufficient for transcriptional activation and that activator-mediated recruitment of TFIID is additionally required for induction of signal-dependent genes.
Nakajima
T
T
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Uchida
C
C
Anderson
S F
SF
Parvin
J D
JD
Montminy
M
M
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000378:metabolism; D015398:Signal Transduction; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII / Q000378:metabolism; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII; D000242:Cyclic AMP; D012319:RNA Polymerase II