TY - JOUR
T1 - c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock factor-1 suppress its transcriptional activity
AU - Dai, Rujuan
AU - Frejtag, Wojciech
AU - He, Bin
AU - Zhang, Yan
AU - Mivechi, Nahid F.
PY - 2000/6/16
Y1 - 2000/6/16
N2 - 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-1 is translocated into the nucleus, forms trimers, acquires DNA binding activity, is hyperphosphorylated, appears as puncrate granules, and increases transcriptional activity of target genes. As cells recover from stress, the puncrate granules gradually disappear, and HSF-1 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-1-driven transcription. Here, we show that c-Jun NH2-terminal kinase (JNK) also phosphorylates and inactivates HSF-1. Overexpression of JNK facilitates the rapid disappearance of HSF-1 punctate granules after heat shock. Similar to ERK, JNK binds to HSF-1 in the conserved mitogenactivated protein kinases binding motifs and phosphorylates HSF-1 in the regulatory domain. The overexpression of an HSF-1-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 from the sites of transcription.
AB - 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-1 is translocated into the nucleus, forms trimers, acquires DNA binding activity, is hyperphosphorylated, appears as puncrate granules, and increases transcriptional activity of target genes. As cells recover from stress, the puncrate granules gradually disappear, and HSF-1 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-1-driven transcription. Here, we show that c-Jun NH2-terminal kinase (JNK) also phosphorylates and inactivates HSF-1. Overexpression of JNK facilitates the rapid disappearance of HSF-1 punctate granules after heat shock. Similar to ERK, JNK binds to HSF-1 in the conserved mitogenactivated protein kinases binding motifs and phosphorylates HSF-1 in the regulatory domain. The overexpression of an HSF-1-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 from the sites of transcription.
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U2 - 10.1074/jbc.M000958200
DO - 10.1074/jbc.M000958200
M3 - Article
C2 - 10747973
AN - SCOPUS:0034674061
SN - 0021-9258
VL - 275
SP - 18210
EP - 18218
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -