A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)

Yoichi Ohiro; Igor Garkavtsev; Shinichiro Kobayashi; Kodangattil R. Sreekumar; Regan Nantz; Bryan T. Higashikubo; Shannon L. Duffy; Ryuji Higashikubo; Anny Usheva; David Gius; Nikolai Kley; Nobuo Horikoshi

doi:10.1016/S0014-5793(02)03049-1

A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)

Yoichi Ohiro, Igor Garkavtsev, Shinichiro Kobayashi, Kodangattil R. Sreekumar, Regan Nantz, Bryan T. Higashikubo, Shannon L. Duffy, Ryuji Higashikubo, Anny Usheva, David Gius, Nikolai Kley, Nobuo Horikoshi

Radiation Oncology

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

Abstract

The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.

Original language	English (US)
Pages (from-to)	163-171
Number of pages	9
Journal	FEBS Letters
Volume	524
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(02)03049-1
State	Published - Jul 31 2002

Keywords

Apoptosis
Cloning
Oxidoreductase
Target gene
Transcription
p53

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0014-5793(02)03049-1

Cite this

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title = "A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)",

abstract = "The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.",

keywords = "Apoptosis, Cloning, Oxidoreductase, Target gene, Transcription, p53",

author = "Yoichi Ohiro and Igor Garkavtsev and Shinichiro Kobayashi and Sreekumar, {Kodangattil R.} and Regan Nantz and Higashikubo, {Bryan T.} and Duffy, {Shannon L.} and Ryuji Higashikubo and Anny Usheva and David Gius and Nikolai Kley and Nobuo Horikoshi",

note = "Funding Information: The authors thank M.J. Romanowski for his critical comments on the manuscript. The authors also thank Q. Qing-Qing for technical assistant. This work was partly supported by Grants from Edward Mallinckrodt Jr. Foundation (N.H.), American Heart Association (9930031, A.U.) and National Institute of Health (HL62458, A.U., CA75556, N.H.).",

year = "2002",

month = jul,

day = "31",

doi = "10.1016/S0014-5793(02)03049-1",

language = "English (US)",

volume = "524",

pages = "163--171",

journal = "FEBS Letters",

issn = "0014-5793",

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number = "1-3",

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TY - JOUR

T1 - A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)

AU - Ohiro, Yoichi

AU - Garkavtsev, Igor

AU - Kobayashi, Shinichiro

AU - Sreekumar, Kodangattil R.

AU - Nantz, Regan

AU - Higashikubo, Bryan T.

AU - Duffy, Shannon L.

AU - Higashikubo, Ryuji

AU - Usheva, Anny

AU - Gius, David

AU - Kley, Nikolai

AU - Horikoshi, Nobuo

N1 - Funding Information: The authors thank M.J. Romanowski for his critical comments on the manuscript. The authors also thank Q. Qing-Qing for technical assistant. This work was partly supported by Grants from Edward Mallinckrodt Jr. Foundation (N.H.), American Heart Association (9930031, A.U.) and National Institute of Health (HL62458, A.U., CA75556, N.H.).

PY - 2002/7/31

Y1 - 2002/7/31

N2 - The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.

AB - The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.

KW - Apoptosis

KW - Cloning

KW - Oxidoreductase

KW - Target gene

KW - Transcription

KW - p53

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U2 - 10.1016/S0014-5793(02)03049-1

DO - 10.1016/S0014-5793(02)03049-1

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AN - SCOPUS:0037205746

SN - 0014-5793

VL - 524

SP - 163

EP - 171

JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -

A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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