NFkappa B-dependent transcriptional activation during heat shock recovery. Thermolability of the NF-kappaB.Ikappa B complex.
Heat shock induces the accumulation of misfolded proteins and results in the preferential expression of heat shock proteins, which help the cell to recover from thermal damage. Heat shock is a well known transcriptional activator of the human immunodeficiency virus type 1 long terminal repeat (LTR). We report here that mutations or deletions of the LTR kappaB sites impaired the LTR transcriptional activation by heat shock. Further analysis revealed that, during heat shock recovery, the NF-kappaB p65 and p50 subunits migrated into the nucleus of HeLa cells, bound to DNA, and induced kappaB-dependent reporter gene expression. This NF-kappaB activation did not depend on new transcriptional and/or translational events and on the pro-oxidant state generated by heat shock. It was not concomitant with IkappaBalpha phosphorylation and was not abolished by the expression of IkappaB kinase or IkappaBalpha dominant-negative mutants. Moreover, NF-kappaB activation and migration into the nucleus were not concomitant with IkappaBalpha/beta or p105 degradation. However, during heat shock recovery, NF-kappaB was dissociated from its complexing partners, allowing its migration into the nucleus. Hence, we describe here a novel mechanism for activation of NF-kappaB based on the thermolability of the NF-kappaB.IkappaB complex.
Kretz-Remy
C
C
Laboratoire Stress Oxydant, Chaperons, et Apoptose, Centre de Génétique Moléculaire et Cellulaire, CNRS-UMR 5534, Université Claude Bernard Lyon I, F-69622 Villeurbanne Cedex, France.
Munsch
B
B
Arrigo
A P
AP
D001483:Base Sequence; D004247:DNA; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D006868:Hydrolysis; D020672:I-kappa B Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D015533:Transcriptional Activation
D020672:I-kappa B Proteins; D016328:NF-kappa B; D004247:DNA