p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis.
Using the differential display method combined with a cell line that carries a well-controlled expression system for wild-type p53, we isolated a p53-inducible gene, termed p53DINP1 (p53-dependent damage-inducible nuclear protein 1). Cell death induced by DNA double-strand breaks (DSBs), as well as Ser46 phosphorylation of p53 and induction of p53AIP1, were blocked when we inhibited expression of p53DINP1 by means of an antisense oligonucleotide. Overexpression of p53DINP1 and DNA damage by DSBs synergistically enhanced Ser46 phosphorylation of p53, induction of p53AIP1 expression, and apoptotic cell death. Furthermore, the protein complex interacting with p53DINP1 was shown to phosphorylate Ser46 of p53. Our results suggest that p53DINP1 may regulate p53-dependent apoptosis through phosphorylation of p53 at Ser46, serving as a cofactor for the putative p53-Ser46 kinase.
Okamura
S
S
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan.
Arakawa
H
H
Tanaka
T
T
Nakanishi
H
H
Ng
C C
CC
Taya
Y
Y
Monden
M
M
Nakamura
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern; D002352:Carrier Proteins; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D005720:Gamma Rays; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006360:Heat-Shock Proteins; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; C414742:P53AIP1 protein, human; D011506:Proteins; D011993:Recombinant Fusion Proteins; C429767:TP53INP1 protein, human; C498965:Trp53inp1 protein, mouse; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin