期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：21
页码：12301-12306
DOI：10.1073/pnas.2133048100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The ZAS proteins are large zinc-finger transcriptional proteins implicated in growth, signal transduction, and lymphoid development. Recombinant ZAS fusion proteins containing one of the two DNA-binding domains have been shown to bind specifically to the {kappa}B motif, but the endogenous ZAS proteins or their physiological functions are largely unknown. The {kappa}B motif, GGGACTTTCC, is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth. The Rel family of NF-{kappa}B, predominantly p65.p50 and p50.p50, are transcription factors well known for inducing gene expression by means of interaction with the {kappa}B motif during acute-phase responses. A functional link between ZAS and NF-{kappa}B, two distinct families of {kappa}B-binding proteins, stems from our previous in vitro studies that show that a representative member, ZAS3, associates with TRAF2, an adaptor molecule in tumor necrosis factor signaling, to inhibit NF-{kappa}B activation. Biochemical and genetic evidence presented herein shows that ZAS3 encodes major {kappa}B-binding proteins in B lymphocytes, and that NF-{kappa}B is constitutively activated in ZAS3-deficient B cells. The data suggest that ZAS3 plays crucial functions in maintaining cellular homeostasis, at least in part by inhibiting NF-{kappa}B by means of three mechanisms: inhibition of nuclear translocation of p65, competition for {kappa}B gene regulatory elements, and repression of target gene transcription.
