C-Jun NH2-Terminal Kinase Targeting and Phosphorylation of Heat Shock Factor-1 Suppress Its Transcriptional Activity

Details

• Personal Author:
  Dai RJ ; Frejtag W ; He B ; Mivechi NF ; Zhang Y
• Description:
  The mammalian heat shock transcription factor HSF-1 regulates the expression of the heat shock proteins, molecular chaperones that are involved in cellular processes from higher order assembly to protein degradation. HSF-1 is a phosphorylated monomer under physiological growth conditions and is located mainly in the cytoplasm. Upon activation by a variety of environmental stresses, HSF-I is translocated into the nucleus, forms trimers, acquires DNA binding activity, is hyperphosphorylated, appears as punctate granules, and increases transcriptional activity of target genes. As cells recover from stress, the punctate granules gradually disappear, and HSF-I appears in a diffused staining pattern in the cytoplasm and nucleus. We have previously shown that the mitogen-activated protein kinase ERK phosphorylates and suppresses HSF-l-driven transcription. Here, Re show that c-Jun NH2-terminal kinase (JNK) also phosphorylates and inactivates HSF-I. Overexpression of JNK facilitates the rapid disappearance of HSF-1 punctate granules after heat shock Similar to ERE, JNK binds to HSF-1 in the conserved mitogen-activated protein kinases binding motifs and phosphorylates HSF-1 in the regulatory domain. The overexpression of an HSF-l-green fluorescent protein fusion construct lacking JNK phosphorylation sites causes this HSF-1 mutant to form nuclear granules that remain longer in the nucleus after heat shock. Taken together, these findings indicate that JNK phosphorylates HSF-1 and suppresses its transcriptional activity by rapidly clearing HSF-1 hom the sites of transcription. [Description provided by NIOSH]
• Subjects:
  Environmental Exposure Environmental Health Environmental Pollution Genetics Heat Stress Disorders Hot Temperature Occupational Health Safety
• Keywords:
  Analytical-methods Analytical-processes Cell-biology Cell-differentiation Cell-function Cell-metabolism Cellular-transport-mechanism Environmental-exposure Environmental-factors Environmental-hazards Genes Genetic-factors Heat Heat-exchange Heat-stress Molecular-biology Physiological-function Physiological-response Physiological-stress Physiology

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• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OD - Office of the Director
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  275
• Issue:
  24
• NIOSHTIC Number:
  nn:20032670
• Citation:
  J Biol Chem 2000 Jun; 275(24):18210-18218
• Contact Point Address:
  NF Mivechi, Institute of Molecular Medicine and Genetics, Gene Regulation Group, and Dept. of Radiology, Medical College of Georgia, 1120 15th St., CB2803, Augusta, GA 30912
• Email:
  mivechi@immag.mcg.edu
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:72a6917899f3d923dbc7850ad8222576774d235bf01f19b16659c085e4fd4555e6f1df30ee5a2278c33138f4c83fe67105530a331765614e5eae316cceba6955
• Download URL:
  https://stacks.cdc.gov/view/cdc/186560/cdc_186560_DS1.pdf
• File Type:
  [PDF - 685.90 KB ]