Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
RETINOBLASTOMA GENE-PRODUCT AS A DOWNSTREAM TARGET FOR A CERAMIDE-DEPENDENT PATHWAY OF GROWTH ARREST
Autore:
DBAIBO GS; PUSHKAREVA MY; JAYADEV S; SCHWARZ JK; HOROWITZ JM; OBIED LM; HANNUN YA;
Indirizzi:
DUKE UNIV,MED CTR,DEPT MED,BOX 3355 DURHAM NC 27710 DUKE UNIV,MED CTR,DEPT MED DURHAM NC 27710 DUKE UNIV,MED CTR,DEPT CELL BIOL DURHAM NC 27710 DUKE UNIV,MED CTR,DEPT PEDIAT DURHAM NC 27710 DUKE UNIV,MED CTR,DEPT MOLEC CANC BIOL DURHAM NC 27710
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 5, volume: 92, anno: 1995,
pagine: 1347 - 1351
SICI:
0027-8424(1995)92:5<1347:RGAADT>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
NECROSIS-FACTOR-ALPHA; ADENOVIRUS E1A PROTEINS; CELL-FREE SYSTEM; SPHINGOMYELIN TURNOVER; SIGNAL-TRANSDUCTION; SUSCEPTIBILITY GENE; TUMOR-ANTIGEN; HL-60 CELLS; SPHINGOSINE; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
G.S. Dbaibo et al., "RETINOBLASTOMA GENE-PRODUCT AS A DOWNSTREAM TARGET FOR A CERAMIDE-DEPENDENT PATHWAY OF GROWTH ARREST", Proceedings of the National Academy of Sciences of the United Statesof America, 92(5), 1995, pp. 1347-1351

Abstract

Ceramide, a lipid mediator, has been most closely associated with antiproliferative activities. In this study, we examine the mechanism by which ceramide induces growth suppression and the role of the retinoblastoma gene product (Rb) in this process, Withdrawal of serum from theserum-dependent MOLT-4 cells resulted in significant dephosphorylation of Rb, correlating with the induction of G(0)/G(1) cell cycle arrest, Serum withdrawal resulted in marked elevation in the levels of endogenous ceramide (3-fold at 24 h and 8-fold at 96 h) with little changesin the endogenous levels of sphingosine. The addition of exogenous C-6-ceramide resulted in a concentration- and time-dependent dephosphorylation of Rb, Exogenous ceramide was active at levels comparable to endogenous levels achieved with serum withdrawal, Peak activity of exogenous ceramide (at 6 h) correlated with the uptake of C-6-ceramide by MOLT-4 cells, Next, a number of studies were conducted to determine whether Rb plays a role in ceramide-induced growth suppression, (i) C-6-Ceramide was poorly active in growth suppression of retinoblastoma cells that lack Rb, (ii) Mink lung epithelial cells in which Rb had been sequestered by overexpression of large tumor antigen were resistant to the action of ceramide compared to cells transfected with large tumor antigen mutated in the Rb-binding pocket, (iii) Overexpression of the E1A adenoviral protein, which binds and sequesters Rb, resulted in protection from growth suppression and cell cycle arrest induced by ceramide, Thus, these studies demonstrate that Rb is a downstream target for ceramide and may function in a growth suppressor pathway resulting in cell cycle arrest.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 06:58:31