Adenovirus DNA binding protein inhibits SrCap-activated CBP and CREB-mediated transcription.
The SNF2-related CBP activator protein (SrCap) is a potent activator of transcription mediated by CBP and CREB. We have previously demonstrated that the Adenovirus 2 DNA Binding Protein (DBP) binds to SrCap and inhibits the transcription mediated by the carboxyl-terminal region of SrCap (amino acids 1275-2971). We report here that DBP inhibits the ability of full-length SrCap (1-2971) to activate transcription mediated by Gal-CREB and Gal-CBP. In addition, DBP also inhibits the ability of SrCap to enhance Protein Kinase A (PKA) activated transcription of the enkaphalin promoter. DBP was found to dramatically inhibit transcription of a mammalian two-hybrid system that was dependent on the interaction of SrCap and CBP binding domains. We also found that DBP has no effect on transcription mediated by a transcriptional activator that is not related to SrCap, indicating that our reported transcriptional inhibition is specific for SrCap and not due to nonspecific effects of DBP's DNA binding activity on the CAT reporter plasmid. Taken together, these results suggest a model in which DBP inhibits cellular transcription mediated by the interaction between SrCap and CBP.
Xu
Xiequn
X
Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, Saint Louis, MO 63104, USA.
Tarakanova
Vera
V
Chrivia
John
J
Yaciuk
Peter
P
D000123:Acetyltransferases / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016466:CHO Cells; D050882:CREB-Binding Protein; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics*
D017362:Cyclic AMP Response Element-Binding Protein; C095599:DBP protein, Adenovirus; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014764:Viral Proteins; D000123:Acetyltransferases; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D000251:Adenosine Triphosphatases; C119652:SRCAP protein, human