Transcriptional coactivator cAMP response element binding protein mediates induction of the human proliferating cell nuclear antigen promoter by the adenovirus E1A oncoprotein

Transcriptional coactivator cAMP response element binding protein mediates induction of the human proliferating cell nuclear antigen promoter by the adenovirus E1A oncoprotein

Benjamin H. Lee*,† and
Michael B. Mathews*

^*Cold Spring Harbor Laboratory, P.O. Box 100, Cold Spring Harbor, NY 11724-2208; and ^†Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11790

Abstract

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.

Footnotes

↵ * To whom reprint requests should be sent at present address: Department of Biochemistry and Molecular Biology, UMDNJ, Newark, NJ 07103.
Michael H. Wigler, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
ABBREVIATIONS:

PCNA,

proliferating cell nuclear antigen;

CREB,

cAMP response element binding protein;

PERE,

PCNA-E1A responsive element;

ATF,

activating transcription factor;

CBP,

CREB-binding protein;

CAT,

chloramphenicol acetyltransferase;

EMSA,

electrophoretic mobility shift assay;

DBD,

DNA-binding domain;

CMV,

cytomegalovirus