Heat shock protein 90 is important for Sp1 stability during mitosis.
Our previous study has revealed that heat shock protein (Hsp) 90 can interact with Sp1 to regulate the transcriptional activity of 12(S)-lipoxygenase. Herein, we further found that the interaction between Hsp90 and Sp1 occurred during mitosis. By geldanamycin (GA) treatment and knockdown of Hsp90, we found that this interaction during mitosis was involved in the maintenance of Sp1 stability, and that the phospho-c-Jun N-terminal kinase (JNK)-1 level also decreased. As the JNK-1 was knocked down by the shRNA of JNK-1, Sp1 was degraded through a ubiquitin-dependent proteasome pathway. In addition, for mutation of the JNK-1 phosphorylated residues of Sp1, namely, Sp1(T278/739A) and Sp1(T278/739D), the effect of GA on Sp1 stability was reversed. Finally, based on the involvement of Hsp90 in Sp1 stability, the transcriptional activities of p21(WAF1/CIP1) and 12(S)-lipoxygenase under GA treatment were observed to have decreased. Taken together, Hsp90 is important for maintaining Sp1 stability during mitosis by the JNK-1-mediated phosphorylation of Sp1 to enable division into daughter cells and to regulate the expression of related genes in the interphase.
Wang
Shao-An
SA
Institute of Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
Chuang
Jian-Ying
JY
Yeh
Shiu-Hwa
SH
Wang
Yi-Ting
YT
Liu
Yi-Wen
YW
Chang
Wen-Chang
WC
Hung
Jan-Jong
JJ
D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001483:Base Sequence; D016227:Benzoquinones / Q000494:pharmacology; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D048055:Mitogen-Activated Protein Kinase 8 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000378:metabolism
D016227:Benzoquinones; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D025801:Ubiquitin; D001092:Arachidonate 12-Lipoxygenase; D048055:Mitogen-Activated Protein Kinase 8; C001277:geldanamycin