CBP alleviates the intramolecular inhibition of ATF-2 function.
The transcription factor ATF-2 (also called CRE-BP1), whose DNA-binding domain consists of a basic amino acid cluster and a leucine zipper (b-ZIP) region, binds to the cAMP response element as a homodimer or as a heterodimer with c-Jun. The amino-terminal region of ATF-2 containing the transcriptional activation domain is phosphorylated by stress-activated kinases, which leads to activation of ATF-2. We report here that CBP, which was originally identified as a co-activator of CREB, directly binds to the b-ZIP region of ATF-2 via a Cys/His-rich region termed C/H2, and potentiates trans-activation by ATF-2. The b-ZIP region of ATF-2 was previously shown to interact with the amino-terminal region intramolecularly and to inhibit trans-activating capacity. The binding of CBP to the b-ZIP region abrogates this intramolecular interaction. The adenovirus 13S E1A protein which binds to the b-ZIP region of ATF-2 also inhibited this intramolecular interaction, suggesting that both CBP and 13S E1A share a similar function as positive regulators of ATF-2. We found that the b-ZIP regions of c-Jun and CREB also interact with the C/H2 domain of CBP, suggesting that CBP acts as a regulator for a group of b-ZIP-containing proteins. These results shed light on a novel aspect of CBP function as a regulator for a group of b-ZIP-containing proteins.
Sano
Y
Y
Laboratory of Molecular Genetics, Tsukuba Life Science Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Tokitou
F
F
Dai
P
P
Maekawa
T
T
Yamamoto
T
T
Ishii
S
S
D051698:Activating Transcription Factor 2; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors*; D004268:DNA-Binding Proteins / Q000378:metabolism; D051790:G-Box Binding Factors; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; D015534:Trans-Activators; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases