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Grimes HL , Chan TO , ZweidlerMcKay PA , Tong B , Tsichlis PN
The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G(1) arrest induced by interleukin-2 withdrawal
Molecular and Cellular Biology. 1996 Nov;16(11) :6263-6272
PMID: ISI:A1996VN82000033   
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Abstract
The Gfi-1 proto-oncogene is activated by provirus insertion in T-cell lymphoma lines selected for interleukin-2 (IL-2) independence in culture and in primary retrovirus-induced thymomas and encodes a nuclear sequence-specific DNA-binding protein, Here we show that Gfi-1 is a position- and orientation-independent active transcriptional repressor, whose activity depends on a 20-amino-acid N-terminal repressor domain, coincident with a nuclear localization motif. The sequence of the Gfi-1 repressor domain is related to the sequence of the repressor domain of Gfi-1B, a Gfi-1-related protein, and to sequences at the N termini of the insulinoma- associated protein, IA-1, the homeobox protein Gsh-1, and the vertebrate but not the Drosophila members of the Snail-Slug protein family (Snail/Gfi-1, SNAG domain), Although not functionally characterized, these SNAG-related sequences are also likely to mediate transcriptional repression. Therefore, the Gfi-1 SNAG domain may be the prototype of a novel family of evolutionarily con:served repressor domains that operate in multiple cell lineages, Gfi-1 overexpression in IL-2-dependent T-cell lines allows the cells to escape from the G(1) arrest induced by IL-2 withdrawal. Since a single point mutation in the SNAG domain (P2A) inhibits both the Gfi-1-mediated transcriptional repression and the G(1) arrest induced by IL-2 starvation, we conclude that the latter depends on the repressor activity of the SNAG domain. Induction of Gfi-1 may therefore contribute to T-cell activation and tumor progression by repressing the expression of genes that inhibit cellular proliferation.
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Times Cited: 48 English Article VN820 MOL CELL BIOL