HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential for mitotic progression.
Previously, heat shock factor 1 (HSF1) had been reported to induce genomic instability and aneuploidy by interaction with Cdc20. Here, we have further examined the functions of HSF1 in the regulation of mitosis. A null mutant or knockdown of HSF1 caused defective mitotic progression. By monitoring chromosomes in living cells, we determined that HSF1 was localized to the centrosome in mitosis and especially to the spindle poles in metaphase. HSF1 was phosphorylated by Plk1 at Ser(216) of the DSGXXS motif during the timing of mitosis and a phospho-defective mutant form of HSF1 inhibited mitotic progression. Phosphorylated HSF1 during spindle pole localization underwent ubiquitin degradation through the SCF(beta-TrCP) pathway. However, binding of HSF1 with Cdc20 stabilized the phosphorylation of HSF1. Moreover, SCF(beta-TrCP)-mediated degradation only occurred when phosphorylated HSF1 was released from Cdc20. HSF1 phosphorylation at Ser(216) occurred in the early mitotic period with simultaneous binding of Cdc20. The interaction of HSF1 with SCF(beta-TrCP) was followed and then the interaction of APC/Cdc20 was subsequently observed. From these findings, it was shown that Plk1 phosphorylates HSF1 in early mitosis and that the binding of phosphorylated HSF1 with Cdc20 and ubiquitin degradation by SCF(beta-TrCP) regulates mitotic progression.
Lee
Yoon-Jin
YJ
Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Kim
Eun-Ho
EH
Lee
Jae Seon
JS
Jeoung
Dooil
D
Bae
Sangwoo
S
Kwon
Seung Hae
SH
Lee
Yun-Sil
YS
D000818:Animals; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D044843:SKP Cullin F-Box Protein Ligases; D014157:Transcription Factors; D025801:Ubiquitin; D000097869:Polo-Like Kinase 1; C577491:Cdc20 protein, mouse; C000619706:HSF1 protein, human