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
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
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.