Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis.
The p53 tumour suppressor promotes cell-cycle arrest or apoptosis in response to cellular stress, such as DNA damage and oncogenesis. This role of p53 is important for its tumour-suppression function and depends, at least in part, on its ability to bind to specific DNA sequences and activate the transcription of target genes. The pathway through which p53 promotes apoptosis is not fully understood. Here we describe a new gene regulated by p53 that encodes a predicted protein of 915 amino acids in mice (910 amino acids in humans), which we have named Pidd. The mouse Pidd cDNA contains a p53 consensus DNA binding sequence upstream of the Pidd-coding region. This sequence element bound to p53 and conferred p53-dependent inducibility on a heterologous reporter gene. Moreover, Pidd RNA was induced by ionizing radiation in a p53-dependent manner and the basal level of Pidd RNA was dependent on Trp53 status. Overexpression of Pidd inhibited cell growth in a p53-like manner by inducing apoptosis. Antisense inhibition of Pidd expression attenuated p53-mediated apoptosis. Our data suggest that Pidd is an effector of p53-dependent apoptosis.
Lin
Y
Y
Ontario Cancer Institute/Princess Margaret Hospital and the Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Ma
W
W
Benchimol
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004307:Dose-Response Relationship, Radiation; D020224:Expressed Sequence Tags; D005622:Friend murine leukemia virus / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D014170:Transformation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002352:Carrier Proteins; D018076:DNA, Complementary; D053418:Death Domain Receptor Signaling Adaptor Proteins; D016376:Oligonucleotides, Antisense; C485896:PIDD1 protein, human; C414729:Pidd1 protein, mouse; D016159:Tumor Suppressor Protein p53; D008156:Luciferases