Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase
Open Access
- 1 February 2001
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 20 (3), 446-456
- https://doi.org/10.1093/emboj/20.3.446
Abstract
Hsp72, a major inducible member of the heat shock protein family, can protect cells against many cellular stresses including heat shock. In our present study, we observed that pretreatment of NIH 3T3 cells with mild heat shock (43°C for 20 min) suppressed UV‐stimulated c‐Jun N‐terminal kinase 1 (JNK1) activity. Constitutively overexpressed Hsp72 also inhibited JNK1 activation in NIH 3T3 cells, whereas it did not affect either SEK1 or MEKK1 activity. Both in vitro binding and kinase studies indicated that Hsp72 bound to JNK1 and that the peptide binding domain of Hsp72 was important to the binding and inhibition of JNK1. In vivo binding between endogenous Hsp72 and JNK1 in NIH 3T3 cells was confirmed by co‐immunoprecipitation. Hsp72 also inhibited JNK‐dependent apoptosis. Hsp72 antisense oligonucleotides blocked Hsp72 production in NIH 3T3 cells in response to mild heat shock and concomitantly abolished the suppressive effect of mild heat shock on UV‐induced JNK activation and apoptosis. Collectively, our data suggest strongly that Hsp72 can modulate stress‐activated signaling by directly inhibiting JNK.Keywords
This publication has 60 references indexed in Scilit:
- The Function of HSP72 in Suppression of c-Jun N-terminal Kinase Activation Can Be Dissociated from Its Role in Prevention of Protein DamageJournal of Biological Chemistry, 1999
- Prior heat stress inhibits apoptosis in adenosine triphosphate-depleted renal tubular cellsKidney International, 1999
- Hsp70 Prevents Activation of Stress KinasesJournal of Biological Chemistry, 1997
- Heat shock protein hsp70 overexpression confers resistance against nitric oxideFEBS Letters, 1996
- The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heatCurrent Biology, 1996
- Signal Transduction Pathways Regulated by Mitogen-activated/Extracellular Response Kinase Kinase Kinase Induce Cell DeathJournal of Biological Chemistry, 1996
- Opposing Effects of ERK and JNK-p38 MAP Kinases on ApoptosisScience, 1995
- Parallel signal processing among mammalian MAPKsTrends in Biochemical Sciences, 1995
- Mutational analysis of the human HSP70 protein: distinct domains for nucleolar localization and adenosine triphosphate binding.The Journal of cell biology, 1989
- 70K heat shock related proteins stimulate protein translocation into microsomesNature, 1988