The Role of Heat Shock Protein 90 during Mitosis

• Main Authors: Shao-AnWang, 王紹安
• Other Authors: Jan-Jong Hung
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/13050763166067099718

博士 === 國立成功大學 === 生物資訊與訊息傳遞研究所 === 101 === Most previous studies on heat shock protein 90 (Hsp90) have focused on the involvement of Hsp90 in the interphase, whereas the role of this protein in the nucleus during mitosis remains largely unclear. Our previous study has revealed that Hsp90 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 an ubiquitin-dependent proteasome pathway. The results indicate that 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. In addition, we also found that the level of the acetylated form of Hsp90 decreased dramatically during mitosis, which indicates more chaperone activity during mitosis. We further probed proteins that interacted with Hsp90 by liquid chromatography/mass spectrometry (LC/MS) and found that nucleolin was one of those interacting proteins during mitosis. The nucleolin level decreased upon geldanamycin treatment, and Hsp90 maintained the cyclin-dependent kinase 1 (CDK1) activity to phosphorylate nucleolin. Our findings indicate that nucleolin stabilized by Hsp90 contributes to the lung tumorigenesis by increasing the level of many tumor-related mRNAs during mitosis. In conclusion, Hsp90 could play an important chaperone role during mitosis, not only in interphase.