Document Detail


Nucleolar localization of TERT is unrelated to telomerase function in human cells.
MedLine Citation:
PMID:  18522991     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Telomerase maintains telomere length and has been implicated in both aging and carcinogenesis of human cells. This enzyme is a specialized ribonucleoprotein (RNP) complex, minimally consisting of two essential components: the protein catalytic subunit TERT (telomerase reverse transcriptase) and the integral RNA moiety TR (telomerase RNA, TERC). Both TERT and TR have been found to localize to nucleoli within the nucleus, leading to the suggestion of nucleoli as the site for telomerase RNP biogenesis in human cells. However, whether this statement is true or not has not yet been convincingly demonstrated. Here, we identify that residues 965-981 of the human TERT polypeptide constitute an active nucleolar-targeting signal (NTS) essential for mediating human TERT nucleolar localization. Mutational inactivation of this NTS completely disrupted TERT nucleolar translocation in both normal and malignant human cells. Most interestingly, such a TERT mutant still retained the capacity to activate telomerase activity, maintain telomere length and extend the life-span of cellular proliferation, as does wild-type TERT, in BJ cells (normal fibroblasts). Therefore, our data suggest that TERT nucleolar localization is unrelated to telomerase function in human cells.
Authors:
Jian Lin; Rui Jin; Bin Zhang; Hao Chen; Yun Xiu Bai; Ping Xun Yang; Su Wen Han; Yao Hua Xie; Pei Tang Huang; Cuifen Huang; Jun Jian Huang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-03
Journal Detail:
Title:  Journal of cell science     Volume:  121     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-20     Completed Date:  2008-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2169-76     Citation Subset:  IM    
Affiliation:
Laboratory of Tumor and Molecular Biology, Beijing Institute of Biotechnology, 27 Taiping Road, Beijing, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Catalytic Domain
Cell Line
Cell Nucleolus / metabolism
Humans
Mice
Nuclear Localization Signals / genetics,  metabolism
RNA / genetics,  metabolism
Ribonucleoproteins / genetics,  metabolism
Sequence Homology, Amino Acid
Telomerase / genetics*,  metabolism*
Telomere / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Nuclear Localization Signals; 0/Ribonucleoproteins; 0/telomerase RNA; 63231-63-0/RNA; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase

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