Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:2.3.1.28 (
chloramphenicol acetyltransferase
)
5,100
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Heat shock transcription factor 1
(
HSF1
) is constitutively expressed in mammalian cells and negatively regulated for DNA binding and transcriptional activity. Upon exposure to heat shock and other forms of chemical and physiological stress, these activities of
HSF1
are rapidly induced. In this report, we demonstrate that constitutive phosphorylation of
HSF1
at serine residues distal to the transcriptional activation domain functions to repress transactivation. Tryptic phosphopeptide analysis of a collection of chimeric GAL4-
HSF1
deletion and point mutants identified a region of constitutive phosphorylation encompassing serine residues 303 and 307. The significance of phosphorylation at serines 303 and 307 in the regulation of
HSF1
transcriptional activity was demonstrated by transient transfection and assay of a
chloramphenicol acetyltransferase
reporter construct. Whereas the transfected wild-type GAL4-
HSF1
chimera is repressed for transcriptional activity and derepressed by heat shock, mutation of serines 303 and 307 to alanine results in derepression to a high level of constitutive activity. Similar results were obtained with mutation of these serine residues in the context of full-length
HSF1
. These data reveal that constitutive phosphorylation of serines 303 and 307 has an important role in the negative regulation of
HSF1
transcriptional activity at control temperatures.
...
PMID:Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation. 912 59
