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GAAP‐1: a transcriptional activator of p53 and IRF‐1 possesses pro‐apoptotic activity
Author(s) -
Lallemand Christophe,
Palmieri Marta,
Blanchard Brigitte,
Meritet JeanFrançois,
Tovey Michael G
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf032
Subject(s) - promoter , transcription factor , transfection , cancer research , biology , gene , activator (genetics) , microbiology and biotechnology , transcription (linguistics) , apoptosis , gene expression , genetics , linguistics , philosophy
The mechanisms that regulate the transcription of the tumour suppressor genes p53 and IRF‐1 are poorly understood. We have characterized a 68‐kDa transcription factor, GAAP‐1 (gatekeeper of apoptosis activating proteins), encoded by an alternative splice product of the PRDII‐BF1 gene, that recognizes a novel regulatory element within the p53 and IRF‐1 promoters. Transfection of U937 cells with GAAP‐1 activates p53 and IRF‐1 expression and leads to apoptosis, whereas over‐expression of GAAP‐1 in K562 cells that lack p53 and IRF‐1 induces cell differentiation. Alterations in the 6p24 locus containing the GAAP‐1 gene are frequent in acute myelogenous leukemia (AML), and AML‐derived cell lines display reduced GAAP‐1 mRNA levels. Together, these results suggest that GAAP‐1 acts as a gatekeeper at a critical point in the tumour suppressor gene pathway.