title: RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer.
abstract: Human cancers utilise telomerase to maintain telomeres and prohibit cell senescence. Human telomerase reverse transcriptase (hTERT), an essential component of this complex, is regulated at the level of gene transcription. Using SILAC-proteomic analysis and molecular studies, we identified the AAA+ ATPase, RuvBl2 as a transcriptional regulator of hTERT and established that this regulation is through cooperation with Ets-2. In colon cancer patients, nuclear expression of RuvBl2 associated with nuclear expression of hTERT, pEts2 and advanced nodal disease (P<0.01, P=0.05 and P=0.03 respectively, n=170). These data firmly implicate RuvBl2 in Ets2 mediated regulation of hTERT in colon cancer which has functional and clinical consequences.
authors.affiliation: Endocrine Oncology Research, Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Padraic
authors.initials: P
authors.lastname: Flavin
authors.forename: Aisling
authors.initials: A
authors.lastname: Redmond
authors.forename: Jean
authors.initials: J
authors.lastname: McBryan
authors.forename: Sinead
authors.initials: S
authors.lastname: Cocchiglia
authors.forename: Paul
authors.initials: P
authors.lastname: Tibbitts
authors.forename: Patrick
authors.initials: P
authors.lastname: Fahy-Browne
authors.forename: Elaine
authors.initials: E
authors.lastname: Kay
authors.forename: Achim
authors.initials: A
authors.lastname: Treumann
authors.forename: Kilian
authors.initials: K
authors.lastname: Perrem
authors.forename: Marie
authors.initials: M
authors.lastname: McIlroy
authors.forename: Arnold D K
authors.initials: AD
authors.lastname: Hill
authors.forename: Leonie S
authors.initials: LS
authors.lastname: Young
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000502:physiology*; D003110:Colonic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D004265:DNA Helicases / Q000502:physiology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D040901:Proteomics; D050787:Proto-Oncogene Protein c-ets-2 / Q000502:physiology*; D019098:Telomerase / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; C494069:ETS2 protein, human; D050787:Proto-Oncogene Protein c-ets-2; C509186:TERT protein, human; D019098:Telomerase; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human