Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Protein phosphatase 1 alpha-mediated stimulation of apoptosis is associated with dephosphorylation of the retinoblastoma protein
Autore:
Wang, RH; Liu, CWY; Avramis, VI; Berndt, N;
Indirizzi:
Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Div Hematol Oncol, LosAngeles, CA 90027 USA Univ So Calif Los Angeles CA USA 90027 ol Oncol, LosAngeles, CA 90027 USA
Titolo Testata:
ONCOGENE
fascicolo: 43, volume: 20, anno: 2001,
pagine: 6111 - 6122
SICI:
0950-9232(20010927)20:43<6111:PP1ASO>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-CYCLE PROGRESSION; INHIBITOR OKADAIC ACID; CATALYTIC SUBUNIT; GENE-PRODUCT; MAMMALIAN-CELLS; PHOSPHORYLATION; DEATH; ACTIVATION; CLEAVAGE; ARREST;
Keywords:
protein phosphatase 1; retinoblastoma protein; caspase; protein phosphorylation; cell cycle; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Berndt, N Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Div Hematol Oncol, 4650 Sunset Blvd, Los Angeles, CA 90027 USA Univ So Calif 4650 Sunset Blvd Los Angeles CA USA 90027 0027 USA
Citazione:
R.H. Wang et al., "Protein phosphatase 1 alpha-mediated stimulation of apoptosis is associated with dephosphorylation of the retinoblastoma protein", ONCOGENE, 20(43), 2001, pp. 6111-6122

Abstract

Protein phosphatase I (PPI) plays important roles in many different aspects of cellular activities including cell cycle control. One important function of PP1 is to activate the retinoblastoma protein pRB. Here we show that pRB is one of PPI's downstream targets during apoptosis. When HL-60 cells synchronized at the G1/S boundary were treated with pro-apoptotic cytosine arabinoside (araC), PP1 alpha protein increased twofold and PP1 activity about 30% within I h. This was followed by pRB dephosphorylation, pRB cleavageby caspases, DNA fragmentation, the appearance of cells with < 2n DNA content and finally, dying and dead cells. In vitro, pRB was protected from caspase-3 digestion by prior Cdk-mediated phosphorylation, whereas PP1 alpha converted phospho-pRB into an efficient substrate for caspase-3. Introduction of active PP1 alpha into HL-60 cells by electroporation was sufficient toinduce characteristics of apoptosis. Similarly, araC-resistant cells, normally unable to die in response to araC, initiated apoptosis when electroporated with active PP1 alpha. This was also accompanied by pRB cleavage. In contrast, introduction of inhibitor-2 delayed the onset of araC-induced apoptosis, whereas concomitant introduction of PP1 alpha and inhibitor-2 completely prevented PP1 alpha -induced apoptosis. These results suggest that dephosphorylation of key proteins by PP1 alpha may be crucial for the initiation of apoptosis and further support the concept of PPI serving as a potential target for anti-cancer therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 01:44:17