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Titolo:
HUMAN PAPILLOMAVIRUS (HPV)-16-E6 SENSITIZES CELLS TO ATRACTYLOSIDE-INDUCED APOPTOSIS - ROLE OF P53, ICE-LIKE PROTEASES AND THE MITOCHONDRIAL PERMEABILITY TRANSITION
Autore:
BROWN J; HIGO H; MCKALIP A; HERMAN B;
Indirizzi:
UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CELL BIOL LAB,CB 7090,232 TAYLOR HALL CHAPEL HILL NC 27599 UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CELL BIOL LAB CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,LINEBERGER CANC RES CTR CHAPEL HILL NC 27599
Titolo Testata:
Journal of cellular biochemistry
fascicolo: 2, volume: 66, anno: 1997,
pagine: 245 - 255
SICI:
0730-2312(1997)66:2<245:HP(SCT>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN FOLLICULAR LYMPHOMA; ADP/ATP CARRIER; CYCLOSPORINE-A; CHROMOSOMAL BREAKPOINT; SV40-TRANSFORMED CELLS; POTENT INHIBITOR; TUMOR-ANTIGEN; TYPE-18 E6; IN-VIVO; DEATH;
Keywords:
P53; HPV; APOPTOSIS; MITOCHONDRIAL PERMEABILITY TRANSITION; ICE-LIKE PROTEASES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
62
Recensione:
Indirizzi per estratti:
Citazione:
J. Brown et al., "HUMAN PAPILLOMAVIRUS (HPV)-16-E6 SENSITIZES CELLS TO ATRACTYLOSIDE-INDUCED APOPTOSIS - ROLE OF P53, ICE-LIKE PROTEASES AND THE MITOCHONDRIAL PERMEABILITY TRANSITION", Journal of cellular biochemistry, 66(2), 1997, pp. 245-255

Abstract

Infection of cervical epithelial cells with certain high risk HPV genotypes is thought to play an etiologic role in the development of cervical cancer. In particular, HPV type 16 and 18 early protein 6 (E6) isthought to contribute to epithelial transformation by binding to the tumor suppressor protein p53, targeting it for rapid proteolysis, resulting in loss of its cell cycle arrest and apoptosis-inducing activities. Recent data indicate that factors responsible for triggering apoptosis reside in the cytoplasm of cells, and not in the nucleus. In particular, the findings that mitochondria are required in certain cell-free models for induction of apoptosis and that bcl-2 is localized to mitochondria have focused attention on the role of the mitochondrial membrane permeability transition (MPT) in apoptosis. Here we present datato indicate that HPV 16 E6 expression sensitizes cells to MPT-inducedapoptosis. We also report that HPV 16 E6 sensitization of cells to MPT-induced apoptosis occurs only in the presence of wildtype (wt) p53 expression. The extent of apoptosis induced by atractyloside (an inducer of the MPT) in normal, temperature-sensitive (ts) p53, and HPV-16 E6transfected J2-3T3 cells, and the HPV expressing cervical carcinoma cell lines SiHa, Hela and CaSki was determined. C33A cells, which express mutant p53 but not HPV, were also exposed to atractyloside in the presence or absence of HPV 16 E6 expression. Dose-dependent apoptosis induced by atractyloside in normal J2-3T3 cells and cervical carcinoma cells was measured by loss of cell viability, nuclear fragmentation and DNA laddering. The sensitivity of cells to atractyloside-induced apoptosis was found to be: HPV 16 E6-J2-3T3 > CaSki > normal-J2-3T3 cellsapproximate to ts p53-J2-3T3 approximate to vector-J2-3T3 cells > Hela > SiHa > C33A approximate to C33A 16 E6. Cyclosporin A (CsA), an inhibitor of the MPT, and ICE-I, a protease inhibitor, provided protection against atractyloside-induced apoptosis. These findings indicate that: 1) high risk HPV 16 E6 protein is capable of sensitizing cells to apoptosis; 2) HPV 16 E6 sensitization of cells to atractyloside-inducedapoptosis occurs in a p53-dependent fashion; 3) the target of HPV 16 E6 sensitization of cells to atractyloside-induced apoptosis is the mitochondria; and 4) HPV 16 E6 sensitization of cells to atroctycoside-induced apoptosis involves an ICE-like protease-sensitive mechanism, regulating the onset of the MPT. These findings constitute the first evidence that mitochondria play a role in HPV 16 E6 modulation of apoptosis. (C) 1997 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 18:13:05