Transcriptional coactivator cAMP response element binding protein mediates induction of the human proliferating cell nuclear antigen promoter by the adenovirus E1A oncoprotein.
The proliferating cell nuclear antigen (PCNA), a crucial component of eukaryotic cell cycle and DNA replication complexes, is induced by the adenovirus E1A 243R oncoprotein through a cis-acting element termed the PERE (PCNA-E1A responsive element). The PERE contains a sequence homologous to an activating transcription factor (ATF) motif, and ATF-1 is a major component of PERE-protein complexes. We have identified a second PERE-binding protein, the cAMP response element binding protein (CREB) transcription factor, which forms heterodimers with ATF-1 at this site. CREB, but not ATF-1, is able to mediate transactivation of a minimal PCNA-chloramphenicol acetyltransferase reporter by E1A 243R. Further analysis revealed that the transcriptional coactivator, the CREB-binding protein (CBP), associates with PERE-related complexes, and that CBP is able to mediate a strong transactivation response to E1A 243R at the PCNA promoter. Experiments conducted with mutants in the E1A or CREB components support a model whereby E1A 243R transactivates the PCNA promoter via a CBP-CREB-PERE pathway. These findings delineate a paradigm by which E1A 243R can target and transactivate specific DNA promoter sequences.
Lee
B H
BH
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11790, USA.
Mathews
M B
MB
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D050882:CREB-Binding Protein; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; C084301:E1A protein 243R, Human adenovirus type 5; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human