title: Heat shock protein 90 stabilizes nucleolin to increase mRNA stability in mitosis.
abstract: Most 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. In this study, we found that the level of the acetylated form of Hsp90 decreased dramatically during mitosis, which indicates more chaperone activity during mitosis. We thus 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 at Thr-641/707. Mutation of Thr-641/707 resulted in the destabilization of nucleolin in mitosis. We globally screened the level of mitotic mRNAs and found that 229 mRNAs decreased during mitosis in the presence of geldanamycin. Furthermore, a bioinformatics tool and an RNA immunoprecipitation assay found that 16 mRNAs, including cadherin and Bcl-xl, were stabilized through the recruitment of nucleolin to the 3'-untranslated regions (3'-UTRs) of those genes. Overall, strong correlations exist between the up-regulation of Hsp90, nucleolin, and the mRNAs related to tumorigenesis of the lung. Our findings thus indicate that nucleolin stabilized by Hsp90 contributes to the lung tumorigenesis by increasing the level of many tumor-related mRNAs during mitosis.
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
authors: Shao-An
authors: SA
authors: Wang
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
authors: Hao-Yi
authors: HY
authors: Li
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan 701, Taiwan.
authors: Tsung-I
authors: TI
authors: Hsu
authors: Department of Chemistry, College of Science, National Cheng-Kung University, Tainan 701, Taiwan.
authors: Shu-Hui
authors: SH
authors: Chen
authors: Department of Chemistry, College of Science, National Cheng-Kung University, Tainan 701, Taiwan.
authors: Chin-Jen
authors: CJ
authors: Wu
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan 701, Taiwan; Center for Infection Disease and Signal Transduction Research, National Cheng-Kung University, Tainan 701, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors: Wen-Chang
authors: WC
authors: Chang
authors: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan; Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan 701, Taiwan; Center for Infection Disease and Signal Transduction Research, National Cheng-Kung University, Tainan 701, Taiwan; Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan 701, Taiwan. Electronic address: petehung@mail.ncku.edu.tw.
authors: Jan-Jong
authors: JJ
authors: Hung
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D013058:Mass Spectrometry / Q000379:methods; D008938:Mitosis; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods; D000097796:Nucleolin
chemical_list: D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D016203:CDC2 Protein Kinase; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D010750:Phosphoproteins; D012313:RNA; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C001277:geldanamycin