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Titolo:
Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosinekinase
Autore:
Kharbanda, S; Kumar, V; Dhar, S; Pandey, P; Chen, C; Majumder, P; Yuan, ZM; Whang, Y; Strauss, W; Pandita, TK; Weaver, D; Kufe, D;
Indirizzi:
Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA HarvardUniv Boston MA USA 02115 Canc Inst, Sch Med, Boston, MA 02115 USA Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA Columbia Univ New York NY USA 10032 tr Radiol Res, New York, NY 10032 USA Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 , Inst Human Genet, Boston, MA 02115 USA Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 h Med, Chapel Hill, NC 27599 USA Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Med, Ctr Blood Res, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Mol Genet & Microbiol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Genet & Microbiol, Boston, MA 02115 USA
Titolo Testata:
CURRENT BIOLOGY
fascicolo: 10, volume: 10, anno: 2000,
pagine: 568 - 575
SICI:
0960-9822(20000518)10:10<568:ROTHTC>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; HUMAN PAPILLOMAVIRUS TYPE-16; ATAXIA-TELANGIECTASIA; DNA-DAMAGE; TUMOR-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; SACCHAROMYCES-CEREVISIAE; IONIZING-RADIATION; APOPTOTIC RESPONSE; CELLULAR-RESPONSE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
70
Recensione:
Indirizzi per estratti:
Indirizzo: Kufe, D Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USAHarvard Univ Boston MA USA 02115 t, Sch Med, Boston, MA 02115 USA
Citazione:
S. Kharbanda et al., "Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosinekinase", CURR BIOL, 10(10), 2000, pp. 568-575

Abstract

Background: Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported a role in cell transformation. How telomerase activity is regulated, however, is largely unknown. Results: We show here that hTERT associates directly with the c-Abl protein tyrosine kinase. We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. Moreover, our findings demonstrate that exposure of cells to ionizing radiation induces tyrosine phosphorylation of hTERT by a c-Abl-dependent mechanism. The functional significance of the c-Abl-hTERT interaction is supported by the demonstration that cells deficient in c-Abl showtelomere lengthening. Conclusions: The ubiquitously expressed c-Abl tyrosine kinase is activatedby DNA double-strand breaks. Our finding of telomere lengthening in c-Abl-deficient cells and the functional interactions between c-Abl and hTERT support a role for c-Abl in the regulation of telomerase function.

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Documento generato il 02/04/20 alle ore 06:25:09