Activation of heat shock transcription factor 1 to a DNA binding form during the G(1)phase of the cell cycle.
The heat shock transcription factor (HSF) genes encode proteins that bind to the heat shock elements (HSE) of stress-inducible genes. We have observed the induction of HSF1, the ubiquitous member of the HSF family from a latent cytoplasmic state to a form competent to bind HSE during early G(1)in HeLa cells in the absence of stress. The induction of DNA-binding HSF1 coincided with a burst in cellular protein synthesis in early G(1)and inhibition of this translational peak prevented the formation of DNA binding-activated HSF1. A potential role for HSF1 in cell cycle regulation was suggested by the finding that cell lines stably overexpressing HSF1 showed an increased proportion of G(1)cells relative to other cell cycle phases. However, in contrast to the effects of heat shock, entry into G(1)did not lead to HSF1 hyperphosphorylation or increased activity of a heat shock promoter-reporter gene and did not cause the induction of heat shock protein 70 expression. Thus HSF1, previously implicated in the heat shock response is activated to a DNA binding from in G(1)under non-stress conditions and may play a role in G(1)regulation that does not involve the transcription of heat shock genes.
Bruce
J L
JL
Department of Adult Oncology, Dana Farber Cancer Institute and Joint Center for Radiation Therapy, JFB 205, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Chen
C
C
Xie
Y
Y
Zhong
R
R
Wang
Y Q
YQ
Stevenson
M A
MA
Calderwood
S K
SK
D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D017930:Genes, Reporter; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007763:Lac Operon; D008156:Luciferases / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D011500:Protein Synthesis Inhibitors; D014157:Transcription Factors; D004247:DNA; D003513:Cycloheximide; D008156:Luciferases