NF-kappa B induces expression of the Bcl-2 homologue A1/Bfl-1 to preferentially suppress chemotherapy-induced apoptosis

Citation
Cy. Wang et al., NF-kappa B induces expression of the Bcl-2 homologue A1/Bfl-1 to preferentially suppress chemotherapy-induced apoptosis, MOL CELL B, 19(9), 1999, pp. 5923-5929
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR AND CELLULAR BIOLOGY
ISSN journal
0270-7306 → ACNP
Volume
19
Issue
9
Year of publication
1999
Pages
5923 - 5929
Database
ISI
SICI code
0270-7306(199909)19:9<5923:NBIEOT>2.0.ZU;2-4
Abstract
Recent evidence indicates that the transcription factor NF-kappa B is a maj or effector of inducible antiapoptotic mechanisms. For example, it was show n that NF-kappa B activation suppresses the activation of caspase 8, the ap ical caspase in tumor necrosis factor (TNF) receptor family signaling casca des, through the transcriptional regulation of certain TRAF and IAP protein s. However, it was unknown whether NF-kappa B controls other key regulatory mechanisms in apoptosis. Here we show that NF-kappa B activation suppresse s mitochondrial release of cytochrome c through the activation of the Bcl-2 family member A1/Bfl-1. The restoration of A1 in NF-kappa B null cells dim inished TNF-induced apoptosis by reducing the release of proapoptotic cytoc hrome c from mitochondria. In addition, A1 potently inhibited etoposide-ind uced apoptosis by inhibiting the release of cytochrome c and by blocking ca spase 3 activation. Our findings demonstrate that A1 is an important antiap optotic gene controlled by NF-kappa B and establish that the prosurvival fu nction of NF-kappa B can be manifested at multiple levels.