2 DISTINCT FORMS OF ACTIVE TRANSCRIPTION FACTOR CREB (CAMP RESPONSE ELEMENT BINDING-PROTEIN)

被引:139
作者
BERKOWITZ, LA [1 ]
GILMAN, MZ [1 ]
机构
[1] COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724
关键词
Alternative splicing; c-fos promoter; DNA-binding proteins; Signal transduction;
D O I
10.1073/pnas.87.14.5258
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mammalian cells express two distinct forms of transcription factor CREB (cAMP response element binding protein) that are apparently the products of alternative splicing of the CREB gene transcript. The two proteins differ by a 14-amino acid serine-rich insertion present in one of the CREB isoforms. We show that both CREB isoforms are expressed in many cell types and mammalian species. Both encode proteins that bind specifically to a cAMP response element in vitro. As expected for proteins of this class, the CREB proteins bind DNA as dimers. Both proteins impart cAMP-regulated transcriptional activity to a heterologous DNA-binding domain, showing that cAMP directly modulates the transcriptional stimulatory activity of CREB. The presence of multiple CREB isoforms with identical DNA-binding specificities but differences in the presumed regulatory domain raises the possibility that CREB proteins may be able to integrate distinct regulatory signals at the level of gene transcription.
引用
收藏
页码:5258 / 5262
页数:5
相关论文
共 26 条
[1]   MULTIPLE SEQUENCE ELEMENTS OF A SINGLE FUNCTIONAL CLASS ARE REQUIRED FOR CYCLIC-AMP RESPONSIVENESS OF THE MOUSE C-FOS PROMOTER [J].
BERKOWITZ, LA ;
RIABOWOL, KT ;
GILMAN, MZ .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (10) :4272-4281
[2]   A CYCLIC AMP- AND PHORBOL ESTER-INDUCIBLE DNA ELEMENT [J].
COMB, M ;
BIRNBERG, NC ;
SEASHOLTZ, A ;
HERBERT, E ;
GOODMAN, HM .
NATURE, 1986, 323 (6086) :353-356
[3]   CYCLIC-AMP AND PHORBOL ESTER-STIMULATED TRANSCRIPTION MEDIATED BY SIMILAR DNA ELEMENTS THAT BIND DISTINCT PROTEINS [J].
DEUTSCH, PJ ;
HOEFFLER, JP ;
JAMESON, JL ;
HABENER, JF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (21) :7922-7926
[4]   BOTH THE BASIC REGION AND THE LEUCINE ZIPPER DOMAIN OF THE CYCLIC-AMP RESPONSE ELEMENT BINDING (CREB) PROTEIN ARE ESSENTIAL FOR TRANSCRIPTIONAL ACTIVATION [J].
DWARKI, VJ ;
MONTMINY, M ;
VERMA, IM .
EMBO JOURNAL, 1990, 9 (01) :225-232
[5]  
EDELMAN AM, 1987, ANN REV BIOCH, V56, P576
[6]   CYCLIC-AMP STIMULATES SOMATOSTATIN GENE-TRANSCRIPTION BY PHOSPHORYLATION OF CREB AT SERINE-133 [J].
GONZALEZ, GA ;
MONTMINY, MR .
CELL, 1989, 59 (04) :675-680
[7]  
GONZALEZ GA, 1989, NATURE, V337, P751
[8]  
GROVE JR, 1987, SCIENCE, V238, P530
[9]   TRANSCRIPTION FACTOR ATF CDNA CLONES - AN EXTENSIVE FAMILY OF LEUCINE ZIPPER PROTEINS ABLE TO SELECTIVELY FORM DNA-BINDING HETERODIMERS [J].
HAI, TW ;
LIU, F ;
COUKOS, WJ ;
GREEN, MR .
GENES & DEVELOPMENT, 1989, 3 (12B) :2083-2090
[10]   ADENOVIRAL CONTROL REGIONS ACTIVATED BY E1A AND THE CAMP RESPONSE ELEMENT BIND TO THE SAME FACTOR [J].
HARDY, S ;
SHENK, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (12) :4171-4175