Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase

Hee Sae Park, Jae Seon Lee, Sung-Ho Huh, Jeong Sun Seo, Eui Ju Choi

Research output: Contribution to journalArticle

244 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)446-456
Number of pages11
JournalEMBO Journal
Volume20
Issue number3
DOIs
StatePublished - Feb 1 2001

Fingerprint

JNK Mitogen-Activated Protein Kinases
NIH 3T3 Cells
Phosphotransferases
Shock
Proteins
Hot Temperature
Chemical activation
Mitogen-Activated Protein Kinase 8
Apoptosis
Antisense Oligonucleotides
Heat-Shock Proteins
Immunoprecipitation
Peptides

Keywords

  • Heat shock protein
  • Hsp72
  • Stress-activated protein kinase
  • c-Jun N-terminal kinase

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. / Park, Hee Sae; Lee, Jae Seon; Huh, Sung-Ho; Seo, Jeong Sun; Choi, Eui Ju.

In: EMBO Journal, Vol. 20, No. 3, 01.02.2001, p. 446-456.

Research output: Contribution to journalArticle

Park, Hee Sae ; Lee, Jae Seon ; Huh, Sung-Ho ; Seo, Jeong Sun ; Choi, Eui Ju. / Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. In: EMBO Journal. 2001 ; Vol. 20, No. 3. pp. 446-456.
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