Zinc-finger Binding Protein-89 (ZBP-89) is a Krüppel-type zinc-finger transcription factor encoded by the human ZNF148 locus on 3q21 or Zfp148 locus on mouse 16B3. It is a ubiquitous protein that typically binds to GC-rich DNA elements, also known to bind Sp1 family members. ZBP-89 functions as both a transcriptional activator and a transcriptional repressor depending on the cell context and gene targets. For example, its binding to the promoters of cyclin-dependent genes such as p21waf1 activates gene expression, while binding to p16INKa suppresses gene expression. In addition, ZBP-89 can exert its effect through protein-protein interactions with p53 or ataxia telangiectasia mutated (ATM). The short-chain fatty acid butyrate induces ZBP-89 expression, suggesting the possibility of direct regulation by normal colonic flora. ZBP-89 induces apoptosis through its ability to repress anti-apoptotic genes Bcl-xL and Mcl-1 while inducing the pro-apoptotic gene Bak. A consequence of its pleomorphic effects is its over-expression in a variety of cancers including those in the liver, stomach, breast, skin, pancreas, and lungs. In addition to its role in cell growth and transformation, ZBP-89 regulates a number of genes involved in inflammation and cooperates with NFκB. ZBP-89 regulates CD11b and in vivo studies demonstrate its essential role in myeloid cell activation. Moreover, ZBP-89 regulates myeloid cell progenitors. In the colon, conditional deletion of the Zfp148 locus in mice has been shown to be essential in maintaining homeostatic levels of tryptophan hydroxylase 1 (Tph1) and anti-microbial peptides required for mucosal defense during infection by Salmonella. In summary, ZBP-89 plays a number of essential roles in various tissues during embryogenesis, homeostasis, inflammation and cancer.
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