Document Detail


C-terminal domain of p16(INK4a) is adequate in inducing cell cycle arrest, growth inhibition and CDK4/6 interaction similar to the full length protein in HT-1080 fibrosarcoma cells.
MedLine Citation:
PMID:  21053367     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The tumor suppressor p16(INK4a) has earned widespread attention in cancer studies since its discovery as an inhibitor of cyclin-dependent kinases (CDKs) 4/6. Structurally, it consists of four complete ankyrin repeats, believed to be involved in CDK4 interaction. According to the previous disparities concerning the importance of domains and inactivating mutations in p16, we aimed to search for the domain possessing the functional properties of the full length protein. Upon our in silico screening analyses followed by experimental assessments, we have identified the novel minimum functional domain of p16 to be the C-terminal half including ankyrin repeats III, IV and the C-terminal flanking region accompanied by loops 2 and 3. Transfection of this truncated form into HT-1080 human fibrosarcoma cells, lacking endogenous p16, revealed that it is able to inhibit cell growth and proliferation equivalent to p16(INK4a). The functional analysis showed that this fragment like p16 can interact with CDK4/6, block the entry into S phase of the cell cycle and suppress growth as indicated by colony formation assay. Identification of p16 minimum functional domain can be of benefit to the future peptidomimetic drug design as well as gene transfer for cancer therapy.
Authors:
Najmeh Fahham; Soroush Sardari; Seyed Nasser Ostad; Behrouz Vaziri; Mohammad Hossein Ghahremani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  111     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-03-22     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1598-606     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
Affiliation:
Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / genetics,  physiology*
Cell Line, Tumor
Cell Survival / genetics,  physiology
Cyclin-Dependent Kinase 4 / genetics,  metabolism*
Cyclin-Dependent Kinase 6 / genetics,  metabolism*
Cyclin-Dependent Kinase Inhibitor p16 / genetics,  metabolism*
Fibrosarcoma / genetics,  metabolism
Humans
Immunoblotting
Immunoprecipitation
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p16; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/CDK6 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinase 6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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