Regulation of epithelial cell growth by ZBP-89: potential relevance in pancreatic cancer.
ZBP-89 (ZNF148) is a Zinc finger Binding Protein of 89 kDa that binds GC-rich DNA elements. Originally, it was expression cloned using a DNA element mediating EGF regulation of the gastrin promoter. ZBP-89 functions as both a transcriptional activator and repressor. A variety of extracellular regulators including TGFbeta, retinoic acid and butyrate stimulate ZBP-89 gene expression. Butyrate activation of p21WAF1 is potentiated by ZBP-89 through the recruitment of the co-activator p300, while chronic stimulation by butyrate increases ZBP-89 gene expression correlating with cell differentiation. ZBP-89 stimulates growth arrest and apoptosis through its ability to bind the p21WAF1 promoter or its ability to form protein-protein interactions with p53. ZBP-89 protein is elevated in a variety of gastrointestinal cancers as well as the pancreas. In particular, ZBP-89 is normally expressed in pancreatic islets and ducts and in about 30% of pancreatic adenocarcinomas.
Bai
Longchuan
L
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Logsdon
Craig
C
Merchant
Juanita L
JL
D000230:Adenocarcinoma / Q000235:genetics* / Q000503:physiopathology*; D017209:Apoptosis; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000494:pharmacology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C110951:ZNF148 protein, human