PMID- 21998300
OWN - NLM
STAT- MEDLINE
DCOM- 20120221
LR  - 20231213
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 51
DP  - 2011 Dec 23
TI  - Heat shock protein 90 stabilizes nucleolin to increase mRNA stability in mitosis.
PG  - 43816-43829
LID - S0021-9258(20)68476-9 [pii]
LID - 10.1074/jbc.M111.310979 [doi]
AB  - 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.
FAU - Wang, Shao-An
AU  - Wang SA
AD  - Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and 
      Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
FAU - Li, Hao-Yi
AU  - Li HY
AD  - Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and 
      Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
FAU - Hsu, Tsung-I
AU  - Hsu TI
AD  - 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.
FAU - Chen, Shu-Hui
AU  - Chen SH
AD  - Department of Chemistry, College of Science, National Cheng-Kung University, 
      Tainan 701, Taiwan.
FAU - Wu, Chin-Jen
AU  - Wu CJ
AD  - Department of Chemistry, College of Science, National Cheng-Kung University, 
      Tainan 701, Taiwan.
FAU - Chang, Wen-Chang
AU  - Chang WC
AD  - 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.
FAU - Hung, Jan-Jong
AU  - Hung JJ
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111013
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Benzoquinones)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - Z3K3VJ16KU (geldanamycin)
SB  - IM
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Benzoquinones/pharmacology
MH  - CDC2 Protein Kinase/*metabolism
MH  - Cell Nucleus/metabolism
MH  - Chromatography, Liquid/methods
MH  - HSP90 Heat-Shock Proteins/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Lactams, Macrocyclic/pharmacology
MH  - Mass Spectrometry/methods
MH  - Mitosis
MH  - Phosphoproteins/chemistry/*metabolism
MH  - Protein Conformation
MH  - RNA/metabolism
MH  - RNA Interference
MH  - RNA, Messenger/metabolism
MH  - RNA-Binding Proteins/chemistry/*metabolism
MH  - Tandem Mass Spectrometry/methods
MH  - Nucleolin
PMC - PMC3243509
EDAT- 2011/10/15 06:00
MHDA- 2012/02/22 06:00
PMCR- 2012/12/23
CRDT- 2011/10/15 06:00
PHST- 2011/10/15 06:00 [entrez]
PHST- 2011/10/15 06:00 [pubmed]
PHST- 2012/02/22 06:00 [medline]
PHST- 2012/12/23 00:00 [pmc-release]
AID - S0021-9258(20)68476-9 [pii]
AID - M111.310979 [pii]
AID - 10.1074/jbc.M111.310979 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Dec 23;286(51):43816-43829. doi: 10.1074/jbc.M111.310979. Epub 
      2011 Oct 13.