GAAP-1: a transcriptional activator of p53 and IRF-1 possesses pro-apoptotic activity.
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.
Lallemand
Christophe
C
Laboratory of Viral Oncology, UPR 9045 CNRS, Institut André Lwoff, F-94801 Villejuif, France.
Palmieri
Marta
M
Blanchard
Brigitte
B
Meritet
Jean-Francois
JF
Tovey
Michael G
MG
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins / Q000502:physiology*; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology; D006801:Humans; D050856:Interferon Regulatory Factor-1; D020014:K562 Cells; D010750:Phosphoproteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D020298:U937 Cells; D016335:Zinc Fingers / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C456586:GAAP-1 protein, human; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53