Document Detail


LIN54 harboring a mutation in CHC domain is localized to the cytoplasm and inhibits cell cycle progression.
MedLine Citation:
PMID:  22895175     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mammalian LIN complex (LINC) plays important roles in regulation of cell cycle genes. LIN54 is an essential core subunit of the LINC and has a DNA binding region (CHC domain), which consists of two cysteine-rich (CXC) domains separated by a short spacer. We generated various LIN54 mutants, such as CHC deletion mutant, and investigated their subcellular localizations and effects on cell cycle. Wild-type LIN54 was predominantly localized in the nucleus. We identified two nuclear localization signals (NLSs), both of which were required for nuclear localization of LIN54. Interestingly, deletion of one CXC domain resulted in an increased cytoplasmic localization. The cytoplasmic LIN54 mutant accumulated in the nucleus after leptomycin B treatment, suggesting CRM1-mediated nuclear export of LIN54. Point mutations (C525Y and C611Y) in conserved cysteine residues of CXC domain that abolish DNA binding activity also increased cytoplasmic localization. These data suggest that DNA binding activity of LIN54 is required for its nuclear retention. We also found that LIN54 (C525Y) and LIN54 (C611Y) inhibited cell cycle progression and led to abnormal nuclear morphology. Other CXC mutants also induced similar abnormalities in cell cycle progression. LIN54 (C525Y) led to a decreased expression of some G2/M genes, whose expressions are regulated by LINC. This cell cycle inhibition was partially restored by overexpression of wild-type LIN54. These results suggest that abnormal cellular localization of LIN54 may have effects on LINC activity.
Authors:
Taira Matsuo; Hiroyo Kuramoto; Tsutomu Kumazaki; Youji Mitsui; Tomoko Takahashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-16
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-13     Completed Date:  2013-02-04     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3227-36     Citation Subset:  IM    
Affiliation:
Laboratory of Physiological Chemistry, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, Kagawa, Japan. t-matsuo@kph.bunri-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Blotting, Western
Cell Cycle / genetics*,  physiology
Cell Line, Tumor
Cytoplasm / metabolism*
DNA Primers / genetics
Flow Cytometry
Green Fluorescent Proteins
Humans
Mice
Microscopy, Fluorescence
Molecular Sequence Data
Mutagenesis, Site-Directed
Nuclear Localization Signals / genetics*
Point Mutation / genetics
Reverse Transcriptase Polymerase Chain Reaction
Sequence Alignment
Trans-Activators / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Lin-54 protein, human; 0/Nuclear Localization Signals; 0/Trans-Activators; 0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins
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