ZBP-89, a Krüppel-like zinc finger protein, inhibits epidermal growth factor induction of the gastrin promoter.
We have shown previously that a GC-rich element (GGGGCGGGGTGGGGGG) conferring epidermal growth factor (EGF) responsiveness to the human gastrin promoter binds Sp1 and additional undefined complexes. A rat GH4 cell line expression library was screened by using a multimer of the gastrin EGF response element, and three overlapping cDNA clones were identified. The full-length rat cDNA encoded an 89-kDa zinc finger protein (ZBP-89) that was 89% identical to a 49-kDa human factor, ht(beta), that binds a GTGGG/CACCC element in T-cell receptor promoters. The conservation of amino acids between the zinc fingers indicates that ZBP-89 is a member of the C2H2 zinc finger family subclass typified by the Drosophila Krüppel protein. ZBP-89 is ubiquitously expressed in normal adult tissues. It binds specifically to the gastrin EGF response element and inhibits EGF induction of the gastrin promoter. Collectively, these results demonstrate that ZBP-89 functions as a repressor of basal and inducible expression of the gastrin gene.
Merchant
J L
JL
Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA. merchanj@umich.edu
Iyer
G R
GR
Taylor
B R
BR
Kitchen
J R
JR
Mortensen
E R
ER
Wang
Z
Z
Flintoft
R J
RJ
Michel
J B
JB
Bassel-Duby
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D005755:Gastrins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D005755:Gastrins; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D004815:Epidermal Growth Factor