A human TERT C-terminal polypeptide sensitizes HeLa cells to H2O2-induced senescence without affecting telomerase enzymatic activity.
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.
Huang
JunJian
J
Department of Molecular Genetics, Beijing Institute of Biotechnology, 27 Taiping Road, Beijing, People's Republic of China. huangjun_j@yahoo.com
Bai
Yun Xiu
YX
Han
Su Wen
SW
Ng
Samuel S M
SS
Jing
Da Dao
DD
Wong
Benjamin C Y
BC
Huang
Cui-fen
CF
Kung
Hsiang-fu
HF
Lin
Marie C M
MC
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*
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