Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
GROWTH SUPPRESSION BY AN E2F-BINDING-DEFECTIVE RETINOBLASTOMA PROTEIN(RB) - CONTRIBUTION FROM THE RB-C POCKET
Autore:
WHITAKER LL; SU HY; BASKARAN R; KNUDSEN ES; WANG JYJ;
Indirizzi:
UNIV CALIF SAN DIEGO,DEPT BIOL,CTR MOL GENET,BONNER HALL 3326,9500 GILMAN DR LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,DEPT BIOL,CTR MOL GENET LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,CTR CANC LA JOLLA CA 92093
Titolo Testata:
Molecular and cellular biology
fascicolo: 7, volume: 18, anno: 1998,
pagine: 4032 - 4042
SICI:
0270-7306(1998)18:7<4032:GSBAER>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
TERMINAL REPEATED DOMAIN; E2F TRANSCRIPTION FACTOR; ABL TYROSINE KINASE; RNA-POLYMERASE-II; CELL-CYCLE; GENE-PRODUCT; PHOSPHORYLATION; IDENTIFICATION; PROLIFERATION; REPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
L.L. Whitaker et al., "GROWTH SUPPRESSION BY AN E2F-BINDING-DEFECTIVE RETINOBLASTOMA PROTEIN(RB) - CONTRIBUTION FROM THE RB-C POCKET", Molecular and cellular biology, 18(7), 1998, pp. 4032-4042

Abstract

Growth suppression by the retinoblastoma protein (RB) is dependent onits ability to form complexes with transcription regulators. At leastthree distinct protein-binding activities have been identified in RB:the large A/B pocket binds E2F, the A/B pocket binds the LXCXE peptide motif, and the C pocket binds the nuclear c-Abl tyrosine kinase, Substitution of Trp for Arg 661 in the B region of RB (mutant 661) inactivates both E2F and LXCXE binding. The tumor suppression function of mutant 661 is not abolished, because this allele predisposes its carriers to retinoblastoma development with a low penetrance. In cell-based assays, 661 is shown to inhibit G(1)/S progression. This low-penetrancemutant also induces terminal growth arrest with reduced but detectable activity. We have constructed mutations that disrupt C pocket activity. When overproduced, the RB C-terminal fragment did not induce terminal growth arrest but could inhibit G(1)/S progression, and this activity was abolished by the C-pocket mutations. In full-length RB, the C-pocket mutations reduced but did not abolish RB function. Interestingly, combination of the C-pocket and 661 mutation's completely abolishedRB's ability to cause an increase in the percentage of cells in G(1) and to induce terminal growth arrest.These results suggest that the A/B or C region can induce a prolongation of G(1) through mechanisms that are independent of each other. In contrast, long-term growth arrest requires combined activities from both regions of RB. In addition, E2Fand LXCXE binding are not the only mechanisms through which RB inhibits cell growth. The C pocket also contributes to RB-mediated growth suppression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 03:44:01