title: A human TERT C-terminal polypeptide sensitizes HeLa cells to H2O2-induced senescence without affecting telomerase enzymatic activity.
abstract: We have constructed a 27-kDa hTERT C-terminal polypeptide (hTERTC27) devoid of domains required for telomerase activity and demonstrated that it is capable of nuclear translocation/telomere-end targeting. Here we showed that expression of a low level of hTERTC27 renders hTERT positive HeLa cells sensitive to H(2)O(2)-induced oxidative stress and subsequent cell senescence. The senescence-associated gene, the cyclin/cdk inhibitor p21(Waf1), was up-regulated. This occurs without changing the expression of endogenous hTERT, causing significant telomere shortening or inhibiting telomerase activity. Results from this study suggest for the first time that in addition to telomerase activity, the C-terminus of hTERT also plays a role in hTERT-mediated cellular resistance to oxidative stress.
authors.affiliation: Department of Molecular Genetics, Beijing Institute of Biotechnology, 27 Taiping Road, Beijing, People's Republic of China. huangjun_j@yahoo.com
authors.forename: JunJian
authors.initials: J
authors.lastname: Huang
authors.forename: Yun Xiu
authors.initials: YX
authors.lastname: Bai
authors.forename: Su Wen
authors.initials: SW
authors.lastname: Han
authors.forename: Samuel S M
authors.initials: SS
authors.lastname: Ng
authors.forename: Da Dao
authors.initials: DD
authors.lastname: Jing
authors.forename: Benjamin C Y
authors.initials: BC
authors.lastname: Wong
authors.forename: Cui-fen
authors.initials: CF
authors.lastname: Huang
authors.forename: Hsiang-fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Marie C M
authors.initials: MC
authors.lastname: Lin
mesh_terms: D016922:Cellular Senescence; D002999:Clone Cells; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D010455:Peptides / Q000235:genetics / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D016877:Oxidants; D010455:Peptides; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; C509186:TERT protein, human; D019098:Telomerase