THE LIM FAMILY TRANSCRIPTION FACTOR-ISL-1 REQUIRES CAMP RESPONSE ELEMENT BINDING-PROTEIN TO PROMOTE SOMATOSTATIN EXPRESSION IN PANCREATIC-ISLET CELLS

被引:111
作者
LEONARD, J [1 ]
SERUP, P [1 ]
GONZALEZ, G [1 ]
EDLUND, T [1 ]
MONTMINY, M [1 ]
机构
[1] UMEA UNIV,DEPT MICROBIOL,S-90187 UMEA,SWEDEN
关键词
CAMP RESPONSE ELEMENT; CELL SPECIFICITY; PHOSPHORYLATION INDEPENDENCE;
D O I
10.1073/pnas.89.14.6247
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
Many eukaryotic genes are regulated by cAMP through a conserved cAMP response element (CRE). Here we show that, in the pancreatic islet cell line Tu6, a well-characterized CRE in the somatostatin gene does not provide cAMP responsiveness but functions as an essential element for its basal activity. DNA-binding and functional analyses indicate that the cAMP-responsive factor CREB regulates somatostatin expression in these cells without requirement for phosphorylation at the protein kinase A-regulated Ser-133 phosphorylation site. In addition to the CRE site, cell-specific expression of the somatostatin gene requires a second promoter element, which binds the recently characterized LIM family protein Isl-1. Thus, Isl-1 and CREB appear to synergize on the somatostatin promoter to stimulate high-level expression in Tu6 cells. The ability of CREB to function in a phosphorylation-independent manner suggests a mechanism by which this protein can regulate gene transcription.
引用
收藏
页码:6247 / 6251
页数:5
相关论文
共 18 条
[1]   THE PITUITARY-SPECIFIC TRANSCRIPTION FACTOR-GHF-1 IS A HOMEOBOX-CONTAINING PROTEIN [J].
BODNER, M ;
CASTRILLO, JL ;
THEILL, LE ;
DEERINCK, T ;
ELLISMAN, M ;
KARIN, M .
CELL, 1988, 55 (03) :505-518
[2]   TISSUE-SPECIFIC ENHANCER OF THE HUMAN GLYCOPROTEIN HORMONE ALPHA-SUBUNIT GENE - DEPENDENCE ON CYCLIC AMP-INDUCIBLE ELEMENTS [J].
DELEGEANE, AM ;
FERLAND, LH ;
MELLON, PL .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (11) :3994-4002
[3]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[4]   NOVEL CYSTEINE-RICH MOTIF AND HOMEODOMAIN IN THE PRODUCT OF THE CAENORHABDITIS-ELEGANS CELL LINEAGE GENE LIN-II [J].
FREYD, G ;
KIM, SK ;
HORVITZ, HR .
NATURE, 1990, 344 (6269) :876-879
[5]   CHARACTERIZATION OF MOTIFS WHICH ARE CRITICAL FOR ACTIVITY OF THE CYCLIC AMP-RESPONSIVE TRANSCRIPTION FACTOR CREB [J].
GONZALEZ, GA ;
MENZEL, P ;
LEONARD, J ;
FISCHER, WH ;
MONTMINY, MR .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (03) :1306-1312
[6]   A CLUSTER OF PHOSPHORYLATION SITES ON THE CYCLIC AMP-REGULATED NUCLEAR FACTOR CREB PREDICTED BY ITS SEQUENCE [J].
GONZALEZ, GA ;
YAMAMOTO, KK ;
FISCHER, WH ;
KARR, D ;
MENZEL, P ;
BIGGS, W ;
VALE, WW ;
MONTMINY, MR .
NATURE, 1989, 337 (6209) :749-752
[7]   CYCLIC-AMP STIMULATES SOMATOSTATIN GENE-TRANSCRIPTION BY PHOSPHORYLATION OF CREB AT SERINE-133 [J].
GONZALEZ, GA ;
MONTMINY, MR .
CELL, 1989, 59 (04) :675-680
[8]   INSULIN GENE ENHANCER BINDING-PROTEIN ISL-1 IS A MEMBER OF A NOVEL CLASS OF PROTEINS CONTAINING BOTH A HOMEODOMAIN AND A CYS-HIS DOMAIN [J].
KARLSSON, O ;
THOR, S ;
NORBERG, T ;
OHLSSON, H ;
EDLUND, T .
NATURE, 1990, 344 (6269) :879-882
[9]   A SPECIFIC MEMBER OF THE ATF TRANSCRIPTION FACTOR FAMILY CAN MEDIATE TRANSCRIPTION ACTIVATION BY THE ADENOVIRUS-E1A PROTEIN [J].
LIU, F ;
GREEN, MR .
CELL, 1990, 61 (07) :1217-1224
[10]   CLONED CELL-LINES FROM A TRANSPLANTABLE ISLET CELL TUMOR ARE HETEROGENEOUS AND EXPRESS CHOLECYSTOKININ IN ADDITION TO ISLET HORMONES [J].
MADSEN, OD ;
LARSSON, LI ;
REHFELD, JF ;
SCHWARTZ, TW ;
LERNMARK, A ;
LABRECQUE, AD ;
STEINER, DF .
JOURNAL OF CELL BIOLOGY, 1986, 103 (05) :2025-2034