Document Detail

Novel splice variants of ING4 and their possible roles in the regulation of cell growth and motility.
MedLine Citation:
PMID:  16973615     Owner:  NLM     Status:  MEDLINE    
The ING4 gene is a candidate tumor suppressor gene that functions in cell proliferation, contact inhibition, and angiogenesis. We identified three novel splice variants of ING4 with differing activities in controlling cell proliferation, cell spreading, and cell migration. ING4_v1 (the longest splice variant), originally identified as ING4, encodes an intact nuclear localization signal (NLS), whereas the other three splice variants (ING4_v2, ING4_v3, and ING4_v4) lack the full NLS, resulting in increased cytoplasmic localization of these proteins. We found that one of the three ING4 variants, ING4_v2, is expressed at the same level as the original ING4 (ING4_v1), suggesting that ING4 variants may have significant biological functions. Growth suppressive effects of the variants that have a partial NLS (ING4_v2 and ING4_v4) were attenuated by a weaker effect of the variants on p21(WAF1) promoter activation. ING4_v4 lost cell spreading and migration suppressive effects; on the other hand, ING4_v2 retained a cell migration suppressive effect but lost a cell spreading suppressive effect. Therefore, ING4_v2, which localized primarily into cytoplasm, might have an important role in the regulation of cell migration. We also found that ING4_v4 played dominant-negative roles in the induction of p21(WAF1) promoter activation and in the suppression of cell motility by ING4_v1. In addition, ING4 variants had different binding affinities to two cytoplasmic proteins, protein-tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha1, and G3BP2a. Understanding the functions of the four splice variants may aid in defining their roles in human carcinogenesis.
Motoko Unoki; Jiang Cheng Shen; Zhi-Ming Zheng; Curtis C Harris
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2006-09-13
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-06     Completed Date:  2006-12-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34677-86     Citation Subset:  IM    
Laboratory of Human Carcinogenesis, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USa.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AB197695;  AB197696;  AB197697
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MeSH Terms
Adaptor Proteins, Signal Transducing
Alternative Splicing*
Blotting, Western
Carrier Proteins / metabolism
Cell Cycle Proteins / genetics*,  metabolism
Cell Movement*
Cell Proliferation*
Colony-Forming Units Assay
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cytoplasm / metabolism
DNA Primers
Fluorescent Antibody Technique, Indirect
Genetic Variation*
Growth Inhibitors / metabolism
Homeodomain Proteins / genetics*,  metabolism
Molecular Sequence Data
NF-kappa B / genetics,  metabolism
Neoplasms / metabolism,  pathology
Nuclear Localization Signals
Phosphoproteins / metabolism
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Tumor Cells, Cultured
Tumor Suppressor Proteins / genetics*,  metabolism
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Carrier Proteins; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA Primers; 0/G3BP protein, human; 0/Growth Inhibitors; 0/Homeodomain Proteins; 0/ING4 protein, human; 0/NF-kappa B; 0/Nuclear Localization Signals; 0/PPFIA1 protein, human; 0/Phosphoproteins; 0/Tumor Suppressor Proteins

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