Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.
Heat shock factor-1 (HSF-1) is the regulator of hsp molecular chaperone transcription, although the intracellular mechanisms involved in HSF-1 activation have not been fully elucidated. As HSF1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase CK2, we have investigated the role of CK2 in HSF1 activation. We demonstrate that HSF-1 is phosphorylated by CK2 on both serine and threonine residues and has characterized a phosphorylation site at threonine 142. Mutation of Thr-142 to alanine (T142A) inhibits trans-activation of the HSP70 gene by HSF1 and in addition inhibits the accumulation of HSF-1 competent to bind heat shock elements in the nucleus. HSF1 activation by heat is correlated with the thermal activation of nuclear CK2 and overexpression of CK2 activates HSF1. Phosphorylation by CK2 on threonine 142 may therefore be an essential step in the thermal activation of latent HSF1 by stresses.
Soncin
Fabrice
F
Centre National de la Recherche Scientifique EP 560, Institut Pasteur de Lille, 1 Rue Calmette-BP 245, 59021, Lille Cedex, France.
Zhang
Xinfeng
X
Chu
Boyang
B
Wang
Xiaozhe
X
Asea
Alexzander
A
Ann Stevenson
Mary
M
Sacks
David B
DB
Calderwood
Stuart K
SK
D000409:Alanine; D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000201:enzymology; D047390:Casein Kinase II; D002417:Cattle; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013912:Threonine; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D011994:Recombinant Proteins; D014157:Transcription Factors; D010769:Phosphothreonine; D013912:Threonine; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D000409:Alanine