AMINO-ACID-ANALOGS ACTIVATE NF-KAPPA-B THROUGH REDOX-DEPENDENT I-KAPPA-B-ALPHA DEGRADATION BY THE PROTEASOME WITHOUT APPARENT I-KAPPA-B-ALPHA PHOSPHORYLATION - CONSEQUENCE ON HIV-1 LONG TERMINAL REPEAT ACTIVATION

Citation
C. Kretzremy et al., AMINO-ACID-ANALOGS ACTIVATE NF-KAPPA-B THROUGH REDOX-DEPENDENT I-KAPPA-B-ALPHA DEGRADATION BY THE PROTEASOME WITHOUT APPARENT I-KAPPA-B-ALPHA PHOSPHORYLATION - CONSEQUENCE ON HIV-1 LONG TERMINAL REPEAT ACTIVATION, The Journal of biological chemistry, 273(6), 1998, pp. 3180-3191
Citations number
86
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
273
Issue
6
Year of publication
1998
Pages
3180 - 3191
Database
ISI
SICI code
0021-9258(1998)273:6<3180:AANTRI>2.0.ZU;2-8
Abstract
We report here that amino acid analogs, which activate hsp70 promoter, are powerful transcriptional activators of human immunodeficiency vir us 1 (HIV-1) long terminal repeat (LTR), an activation which was impai red when the two kappa B sites present in the LTR were mutated or dele ted. Amino acid analogs also stimulated the transcription of a kappa B -controlled reporter gene. Upon treatment with amino acid analogs, the two NF-kappa B subunits (p65 and p50), which are characterized by a r elatively long half-life, redistributed into the nucleus where they bo und to kappa B elements. This phenomenon, which began to be detectable after 1 h of treatment, was concomitant with the degradation of the s hort lived inhibitory subunit I kappa B-alpha by the proteasome. Howev er, contrasting with other NF-kappa B inducers that trigger I kappa B- alpha degradation through a phosphorylation step, amino acid analogs d id not change I kappa B-alpha isoform composition. Antioxidant conditi ons inhibited amino acid analog stimulatory action toward NF-kappa B. This suggests that aberrant protein conformation probably generates a prooxidant state that is necessary for I kappa B-alpha proteolysis by the proteasome. Moreover, this activation of NF-kappa B appeared diffe rent from that mediated by endoplasmic reticulum overload as it was no t inhibited by calcium chelation.