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Titolo:
Transcriptional modulation of the anti-apoptotic protein BCL-XL by the paired box transcription factors PAX3 and PAX3/FKHR
Autore:
Margue, CM; Bernasconi, M; Barr, FG; Schafer, BW;
Indirizzi:
Univ Zurich, Div Clin Chem & Biochem, CH-8032 Zurich, Switzerland Univ Zurich Zurich Switzerland CH-8032 chem, CH-8032 Zurich, Switzerland ETH Zurich, Inst Biochem, Zurich, Switzerland ETH Zurich Zurich Switzerland Zurich, Inst Biochem, Zurich, Switzerland Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA UnivPenn Philadelphia PA USA 19104 & Lab Med, Philadelphia, PA 19104 USA
Titolo Testata:
ONCOGENE
fascicolo: 25, volume: 19, anno: 2000,
pagine: 2921 - 2929
SICI:
0950-9232(20000608)19:25<2921:TMOTAP>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
PAX3-FKHR FUSION PROTEIN; ALVEOLAR RHABDOMYOSARCOMA; MUSCLE DEVELOPMENT; CELL-SURVIVAL; GENES; EXPRESSION; DIFFERENTIATION; DOMAIN; MYOD; DNA;
Keywords:
apoptosis; BCL-XL; PAX transcription factors; rhabdomyosarcoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Schafer, BW Univ Zurich, Div Clin Chem & Biochem, Steinwiesstr 75, CH-8032Zurich, Switzerland Univ Zurich Steinwiesstr 75 Zurich Switzerland CH-8032 erland
Citazione:
C.M. Margue et al., "Transcriptional modulation of the anti-apoptotic protein BCL-XL by the paired box transcription factors PAX3 and PAX3/FKHR", ONCOGENE, 19(25), 2000, pp. 2921-2929

Abstract

The aberrant expression of the transcription factors PAN3 and PAX3/FKHR associated with rhabdomyosarcoma (RMS), solid tumors displaying muscle cell features, suggests that these proteins play an important role in the pathogenesis of RMS. We could previously demonstrate that one of the oncogenic functions of PAS3 and PAX3/FKHR in RMS is protection from apoptosis, BCL-XL isa prominent anti-apoptotic protein present in normal skeletal muscle and RMS cells. In the present study, we establish that BCL-XL is transcriptionally modulated bai PAX3 and PAX3/FMHR, since enhanced expression of both PAX proteins stimulates transcription of endogenous BCL-XL mRNA in a cell type specific manner. Further, we present evidence that both PAX3 and PAX3/FKHR can transcriptionally activate the Bcl-x gene promoter in cotransfection assays. Using electrophoretic mobility shift assays, an ATTA binding site forPAX3 and PAX3/FKHR could be localized in the upstream promoter region (position -42 to -39), Finally, ectopic overexpression of either PAY3, PAX3/FKHR or BCL-XL can rescue tumor cells from apoptosis induced by antisense treatment. These results suggest that at least part of the anti-apoptotic effect of PAX3 and PAX3/FKHR is mediated through direct transcriptional modulation of the prominent anti-apoptotic protein BCL-XL.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 22:44:54