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Titolo:
MUTATIONS INCREASING AUTOINHIBITION INACTIVATE TUMOR SUPPRESSORS SMAD2 AND SMAD4
Autore:
HATA A; LO RS; WOTTON D; LAGNA G; MASSAGUE J;
Indirizzi:
ROCKEFELLER UNIV,CELL BIOL LAB,1230 YORK AVE NEW YORK NY 10021 ROCKEFELLER UNIV,CELL BIOL LAB NEW YORK NY 10021 ROCKEFELLER UNIV,HOWARD HUGHES MED INST,MEM SLOAN KETTERING CANC CTR NEW YORK NY 10021 ROCKEFELLER UNIV,MOL EMBRYOL LAB NEW YORK NY 10021
Titolo Testata:
Nature
fascicolo: 6637, volume: 388, anno: 1997,
pagine: 82 - 87
SICI:
0028-0836(1997)388:6637<82:MIAITS>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
A. Hata et al., "MUTATIONS INCREASING AUTOINHIBITION INACTIVATE TUMOR SUPPRESSORS SMAD2 AND SMAD4", Nature, 388(6637), 1997, pp. 82-87

Abstract

Smad2 and Smad4 are related tumour-suppressor proteins(1,2), which, when stimulated by the growth factor TGF-beta, form a complex to inhibit growth(3). The effector function of Smad2 and Smad4 is located in the conserved carboxy-terminal domain (C domain) of these proteins and is inhibited by the presence of their amino-terminal domains (N domain)(4,5). This inhibitory function of the N domain is shown here to involve an interaction with the C domain that prevents the association of Smad2 with Smad4. This inhibitory function is increased in tumour-derived forms of Smad2 and 4 that carry a missense mutation in a conserved N domain arginine residue. The mutant N domains have an increased affinity for their respective C domains, inhibit the Smad2-Smad4 interaction, and prevent TGF beta-induced Smad2-Smad4 association and signalling. Whereas mutations in the C domain disrupt the effector function of the Smad proteins, N-domain arginine mutations inhibit SMAD signallingthrough a g-ain of autoinhibitory function. Gain of autoinhibitory function isa new mechanism for inactivating tumour suppressors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/21 alle ore 17:00:04