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Grimes HL , Gilks CB , Chan TO , Porter S , Tsichlis PN
The Gfi-1 protooncoprotein represses Bax expression and inhibits T-cell death
Proceedings of the National Academy of Sciences of the United States of America. 1996 Dec 10;93(25) :14569-14573
AbstractThe Gfi-1 protooncogene encodes a nuclear zinc-finger protein that carries a novel repressor domain, SNAG, and functions as a position- and orientation-independent active transcriptional repressor, The Gfi-1 repressor allows interleukin 2 (IL-2)- dependent T cells to escape G(1) arrest induced by IL-2 withdrawal in culture and collaborates with c-myc and pim-1 for the induction of retrovirus-induced lymphomas in animals, Here we show that overexpression of Gfi-1 also inhibits cell death induced by cultivation of IL-2-dependent T-cell lines in IL-2- deficient media. Similarly, induction of Gfi-1 in primary thymocytes from mice carrying a metal-inducible Gfi-1 transgene inhibits cell death induced by cultivation in vitro. The protein and mRNA levels of the proapoptotic regulator Bax are down-regulated by Gfi-1 in both immortalized T-cell lines and primary transgenic thymocytes. The repression is direct and depends on several Gfi-1-binding sites in the p53-inducible Bax promoter, In addition to Bax, Gfi-1 also represses Bak, another apoptosis-promoting member of the Bcl-2 gene family. Therefore, Gfi-1 mag inhibit apoptosis by means of its repression of multiple proapoptotic regulators, The antiapoptotic properties of Gfi-1 provide a potential explanation for its strong collaboration with c-myc during oncogenesis.
NotesTimes Cited: 35 English Article VY448 PROC NAT ACAD SCI USA