p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis

S Okamura; H Arakawa; T Tanaka; H Nakanishi; C C Ng; Y Taya; M Monden; Y Nakamura

doi:10.1016/s1097-2765(01)00284-2

p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis

Mol Cell. 2001 Jul;8(1):85-94. doi: 10.1016/s1097-2765(01)00284-2.

Authors

S Okamura¹, H Arakawa, T Tanaka, H Nakanishi, C C Ng, Y Taya, M Monden, Y Nakamura

Affiliation

¹ Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan.

PMID: 11511362
DOI: 10.1016/s1097-2765(01)00284-2

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Apoptosis / physiology*
Apoptosis Regulatory Proteins
Blotting, Northern
Carrier Proteins*
DNA Damage
Doxorubicin / pharmacology
Gamma Rays
Gene Expression Regulation
Genes, Reporter
Heat-Shock Proteins*
Humans
In Situ Nick-End Labeling
Mice
Microscopy, Fluorescence
Models, Biological
Molecular Sequence Data
Nuclear Proteins / chemistry
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Oligonucleotides, Antisense / metabolism
Phosphorylation
Protein Binding
Proteins / genetics
Proteins / metabolism*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
Ultraviolet Rays

Substances

Antineoplastic Agents
Apoptosis Regulatory Proteins
Carrier Proteins
Heat-Shock Proteins
Nuclear Proteins
Oligonucleotides, Antisense
P53AIP1 protein, human
Proteins
Recombinant Fusion Proteins
TP53INP1 protein, human
Trp53inp1 protein, mouse
Tumor Suppressor Protein p53
Doxorubicin

Associated data

GENBANK/AB017926
GENBANK/AB017927
GENBANK/AB062056