title: Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase.
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 show telomere lengthening.
  
  
  CONCLUSIONS
  The ubiquitously expressed c-Abl tyrosine kinase is activated by 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.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: S
authors.initials: S
authors.lastname: Dhar
authors.forename: P
authors.initials: P
authors.lastname: Pandey
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Majumder
authors.forename: Z M
authors.initials: ZM
authors.lastname: Yuan
authors.forename: Y
authors.initials: Y
authors.lastname: Whang
authors.forename: W
authors.initials: W
authors.lastname: Strauss
authors.forename: T K
authors.initials: TK
authors.lastname: Pandita
authors.forename: D
authors.initials: D
authors.lastname: Weaver
authors.forename: D
authors.initials: D
authors.lastname: Kufe
mesh_terms: D020134:Catalytic Domain; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015151:Immunoblotting; D010766:Phosphorylation; D011233:Precipitin Tests; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D012313:RNA; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000502:physiology; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D016315:Proto-Oncogene Proteins c-abl; D019098:Telomerase