THE CAMP RESPONSE ELEMENT-BINDING PROTEIN SYNERGIZES WITH OTHER TRANSCRIPTION FACTORS TO MEDIATE CAMP RESPONSIVENESS

被引:76
作者
ROESLER, WJ [1 ]
GRAHAM, JG [1 ]
KOLEN, R [1 ]
KLEMM, DJ [1 ]
MCFIE, PJ [1 ]
机构
[1] NATL JEWISH CTR IMMUNOL & RESP MED,DIV BASIC SCI,DENVER,CO 80206
关键词
D O I
10.1074/jbc.270.14.8225
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cAMP responsiveness of the promoter for phosphoenolpyruvate carboxykinase (EC 4.1.1.32) is mediated by a synergistic interaction between a complex regulatory region, which binds liver-enriched transcription factors, and a typical cAMP response element (CRE). Although a role for the CRE-binding protein (CREB) in the cAMP-responsiveness of this promoter has been generally assumed, some uncertainty remains due to the observations that several C/EBP-related proteins bind with near equal affinity, relative to CREB, to this particular CRE. Thus, a detailed analysis of the involvement of CREB in this synergism was undertaken in HepG2 cells. Gel mobility shift assays demonstrate that a CRE probe is bound by CREB present in HepG2 cells. Furthermore, we show that a dominant repressor of CREB is able to significantly reduce the cAMP responsiveness of the PEPCK promoter in HepG2 cells. Finally, we demonstrate using a GAL4-CREB fusion protein that CREB is able to synergize with the liver-enriched factors bound upstream on the PEPCK promoter to mediate a liver-specific response to cAMP. Examination of several mutant forms of CREB allow us to conclude that the ''synergy'' domain of CREB resides within amino acid residues 83-203, and that residues 83-145 can mediate a partial synergistic response. This study establishes that CREB is able to synergize with liver-enriched transcription factors to mediate a tissue-specific response to cAMP.
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页码:8225 / 8232
页数:8
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