WW domain-containing FBP-30 is regulated by p53.
A subtractive cloning approach was used to clone genes transcriptionally induced in thymocytes undergoing programmed cell death after gamma-irradiation. We thus identified about 60 upregulated genes. One of these genes encodes a WW domain previously briefly reported by others, which defines this gene as FBP-30. cDNA sequencing showed FBP-30 to be remarkably conserved in mammals. FBP-30 expression, essentially restricted to T cells, was regulated by p53 since it increased (1) after gamma-irradiation in wild-type but not in p53-/- thymocytes and (2) in cells transfected with a conditional temperature-sensitive p53 mutant, less than 1 h after shifting to permissive temperature. Upregulation of FBP-30 expression thus depends upon p53 protein expression and correlates with cell death induction in these systems. While the kinetics of its induction are rapid, the observed increased expression of FBP-30 in the presence of protein synthesis inhibitors suggests that FBP-30 gene expression is indirectly regulated by p53, through downregulation of a labile inhibitor of FBP-30 expression.
Depraetere
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Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France.
Golstein
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary; D005260:Female; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013950:Thymus Gland / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002352:Carrier Proteins; D018076:DNA, Complementary; C485727:FNBP4 protein, human; C402285:Fnbp4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53