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Differential processing of heat shock factor‐1 at febrile range temperature
Author(s) -
Gupta Aditi,
Wang SanXia,
He JuRen,
Hasday Jeffrey D,
Singh Ishwar S
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a250-b
Subject(s) - phosphorylation , p38 mitogen activated protein kinases , heat shock factor , transcription factor , kinase , hsf1 , microbiology and biotechnology , activator (genetics) , repressor , chemistry , heat shock , mapk/erk pathway , heat shock protein , biology , hsp70 , biochemistry , gene
Heat shock factor‐1 (HSF‐1) is the predominant stress‐activated transcription factor that undergoes stress‐induced trimerization, phosphorylation and nuclear translocation to regulate transcription. Although characterized as an activator of heat shock protein genes, we showed that HSF‐1 could also act as a repressor of bacterial LPS‐induced TNF alpha transcription at febrile range temperature (FRT, 39.5°C). In the present study we determined the effect of FRT on LPS‐induced phosphorylation of HSF‐1 in the murine macrophage RAW 264.7 cells. LPS caused a marked phosphorylation dependent shift in the mobility of HSF‐1 at both 37° and 39.5° C (FRT) within 15 min but the effect subsided by 1h followed by a second phosphorylation of HSF‐1 that occurred by 2h but only in cells that were exposed to FRT. We further noted that the initial shift occurred in HSF‐1 present in the cytosol whereas the later phosphorylation occurred in HSF‐1 present preferentially in the nuclear fraction. ERK and p38 MAP kinases and their downstream kinases RSK and MAPKAP‐k2 were also activated by LPS at both 37° and 39.5° C but the activation pattern was different at the two temperatures. Furthermore, inhibitors of MAP kinases blocked the initial HSF‐1 phosphorylation event but not the later one. We propose that HSF‐1 is diferentially phosphorylated by LPS at FRT and these phosphorylation events regulates its activity as a repressor of transcription.