Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Differential post-translational modification of the tumour suppressor proteins Rb and p53 modulate the rates of radiation-induced apoptosis in vivo
Autore:
Wallace, M; Coates, PJ; Wright, EG; Ball, KL;
Indirizzi:
Univ Dundee, Sch Med, Dept Surg & Mol Oncol, CRC Labs, Dundee DD1 9SY, Scotland Univ Dundee Dundee Scotland DD1 9SY , CRC Labs, Dundee DD1 9SY, Scotland Univ Dundee, Sch Med, Dept Mol & Cellular Pharmacol, Dundee DD1 9SY, Scotland Univ Dundee Dundee Scotland DD1 9SY Pharmacol, Dundee DD1 9SY, Scotland
Titolo Testata:
ONCOGENE
fascicolo: 28, volume: 20, anno: 2001,
pagine: 3597 - 3608
SICI:
0950-9232(20010621)20:28<3597:DPMOTT>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-CYCLE ARREST; RETINOBLASTOMA GENE-PRODUCT; DRUG-RESISTANT CELLS; HUMAN CANCER-CELLS; DNA-DAMAGE; P53-MEDIATED APOPTOSIS; THYMOCYTE APOPTOSIS; MEDIATED APOPTOSIS; HEPATOMA-CELLS; G(1) ARREST;
Keywords:
Rb; p21; p53; apoptosis; genetic variation; radiation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Ball, KL Univ Dundee, Sch Med, Dept Surg & Mol Oncol, CRC Labs, Dundee DD19SY, Scotland Univ Dundee Dundee Scotland DD1 9SY s, Dundee DD1 9SY, Scotland
Citazione:
M. Wallace et al., "Differential post-translational modification of the tumour suppressor proteins Rb and p53 modulate the rates of radiation-induced apoptosis in vivo", ONCOGENE, 20(28), 2001, pp. 3597-3608

Abstract

Ionizing radiation induces p53-dependent apoptosis in the spleen, providing a model system to study p53 regulated events in a normal cell type. We have developed an in vivo model that identifies genetic differences in the regulation of p53-mediated apoptosis and addresses whether altered post-translational events in the p53-p21/Rb axis modulate the sensitivity of cells toradiation-induced cell death in vivo. Splenocytes from mice with distinct genetic backgrounds (DBA/2 and C57BL/6) exhibit differences in the rate of apoptosis, Whilst no obvious strain differences in protein levels of Bcl-2 or the cyclin-CDKs were observed, early posttranslational regulatory eventsin the p53-p21/Rb axis showed striking differences in the two mouse strains. Cells from C57BL/6 animals undergo more rapid apoptosis after irradiation resulting from elevated levels and rapid induction of p53, pronounced Rb-cleavage, and the absence of a sustained induction of p21, In contrast, cells from DBA/2 animals have a reduced rate of apoptosis following irradiation with elevated levels of hyperphosphorylated Rb and a sustained induction of the p21 protein that is coincident with the C-terminal phosphorylation of p53, These data suggest that quantitative differences in the level of p21protein can affect the rate of apoptosis in vivo, consistent with the viewthat p21 is an anti-apoptotic effector of p53, However, striking differences in the Rb protein-caspase cleavage or hyperphosphorylation - in the samecell type, but in different genetic backgrounds, demonstrates that p53-dependent apoptosis can be modulated in vivo by genetic factors that impinge upon the pro- or antiapoptotic potential of Rh, In addition, we show that Rbcleavage is p53-dependent and that its phosphorylation status can be uncoupled from p21 expression. This study highlights the possibility that genetic factors can be identified that affect differential sensitivity of cells to ionizing radiation in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 05:41:51