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.
Mesh Terms:
Arachidonate 12-Lipoxygenase, Base Sequence, Benzoquinones, Cell Line, Cyclin-Dependent Kinase Inhibitor p21, DNA Primers, HSP90 Heat-Shock Proteins, HeLa Cells, Humans, Lactams, Macrocyclic, Mitogen-Activated Protein Kinase 8, Mitosis, Models, Biological, Mutagenesis, Site-Directed, Phosphorylation, Protein Interaction Domains and Motifs, RNA Interference, Recombinant Fusion Proteins, Sp1 Transcription Factor, Transcription, Genetic, Transcriptional Activation, Ubiquitin
Arachidonate 12-Lipoxygenase, Base Sequence, Benzoquinones, Cell Line, Cyclin-Dependent Kinase Inhibitor p21, DNA Primers, HSP90 Heat-Shock Proteins, HeLa Cells, Humans, Lactams, Macrocyclic, Mitogen-Activated Protein Kinase 8, Mitosis, Models, Biological, Mutagenesis, Site-Directed, Phosphorylation, Protein Interaction Domains and Motifs, RNA Interference, Recombinant Fusion Proteins, Sp1 Transcription Factor, Transcription, Genetic, Transcriptional Activation, Ubiquitin
J. Mol. Biol.
Date: Apr. 17, 2009
PubMed ID: 19245816
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- Interactions 3
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