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Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis

SciencePublished 12 May 2000
Eri Oda, Rieko Ohki, Hideki Murasawa, Jiro Nemoto, Tsukasa Shibue, Toshiharu Yamashita
Citations2,086
SJR quartileQ1
SJR score10.42
SNIP6.62

TL;DR

A previously unidentified pro-apoptotic gene, Noxa, which encodes a Bcl-2 homology 3 (BH3)-only member of the BCl-2 family of proteins may represent a mediator of p53-dependent apoptosis.

Abstract

A critical function of tumor suppressor p53 is the induction of apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa. Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family of proteins; this member contains the BH3 region but not other BH domains. When ectopically expressed, Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis.

Keywords

MedicineBiochemistry, Genetics and Molecular Biology