A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF).
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.
Ohiro
Yoichi
Y
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Garkavtsev
Igor
I
Kobayashi
Shinichiro
S
Sreekumar
Kodangattil R
KR
Nantz
Regan
R
Higashikubo
Bryan T
BT
Duffy
Shannon L
SL
Higashikubo
Ryuji
R
Usheva
Anny
A
Gius
David
D
Kley
Nikolai
N
Horikoshi
Nobuo
N
D000244:Adenosine Diphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001665:Binding Sites; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003001:Cloning, Molecular; D004247:DNA; D005420:Flavoproteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D017930:Genes, Reporter; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C494829:AIFM1 protein, human; C462504:ferroptosis suppressor protein 1, human; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D005420:Flavoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000244:Adenosine Diphosphate; D004247:DNA