ZBP-89, a Krüppel-Like Zinc Finger Protein, Inhibits Epidermal Growth Factor Induction of the Gastrin Promoter

Abstract

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.

ZBP-89-induced apoptosis is p53-independent and requires JNK

“…16 Monoclonal antibodies against phospho-ERK1/2, phospho-p38, phospho-JNK1/2, phospho-Elk1, phospho-ATF2 and caspase-8, and polyclonal antibodies against ERK1/2, p38, JNK, c-Jun, phospho-c-Jun, cleaved PARP, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9 and Bid were obtained from Cell Signaling (Beverly, MA, USA). The monoclonal Flag M2 antibody was purchased from Sigma (St Louis, MO, USA).…”

“…6,14,15 ZBP-89 (ZNF148, Zfp148) is a Krü ppel-type zinc-finger protein that is ubiquitously expressed. 16 Recent studies have revealed that ZBP-89 possesses multiple functions, including transcriptional regulation of a variety of genes, 17 cell growth arrest 18,19 and cell death. 18 ZBP-89 expression is highest at the villus tip where apoptotic mature enterocytes are sloughed into the lumen.…”

Expression of ZNF148 in different developing stages of colorectal cancer and its prognostic value

“…[3][4][5][6][7] ZNF148 is universally expressed at low levels in most tissues, 8 including those in the gastrointestinal tract. 9 ZNF148 is a multifunctional transcription factor associated with signaling pathways upstream of cellular proliferation, embryogenesis, differentiation, growth arrest, and apoptosis.…”

Identification and Characterization of a Transcriptional Regulator for the lck Proximal Promoter

“…Mt␤ (identical to BFCOL1, BERF-1) and its human and rat homologues (ht␤, ZBP-89, ZFP148) are reported to bind regulatory regions of various genes, such as the V␤8.1 promoter and the V␣ silencer of the T-cell receptor genes (17), the gastrin promoter (29), the type I collagen promoter (27), the ␤-enolase enhancer (28), the ornithine decarboxylase promoter (30), the p21WAF1 promoter (31), the matrix metalloproteinase-3 promoter (32), the pT␣ enhancer (33), and the silencer element of the vimentin gene (34). Our data showing that mt␤ is ubiquitously expressed at both mRNA and protein levels are consistent with previously published reports and the fact that mt␤ functions in the various promoters and enhancers in various tissues.…”

“…During this study, several cDNAs that have identical sequences with mt␤ have been reported: BFCOL1 that binds to the proximal promoters of the type I collagen genes (27) and BERF-1, a 89-kDa protein that binds to a muscle-specific enhancer of the ␤-enolase gene (28). In addition, the rat and human homologue of the protein, ZBP-89, has been shown to bind to promoter regions of the gastrin gene (29) and the ornithine decarboxylase promoter (30). It has subsequently been reported that the same zinc finger protein also binds to the p21WAF1 gene (31), the matrix metalloproteinase-3 gene (32), the pT␣ gene (33), and the vimentin gene (34).…”