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Titolo:
Functional analysis of human Smad1: Role of the amino-terminal domain
Autore:
Xu, RH; Lechleider, RJ; Shih, HM; Hao, CF; Sredni, D; Roberts, AB; Kung, HF;
Indirizzi:
NCI,rograms,ck Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support P NCI Frederick MD USA 21702 Ctr, SAIC Frederick, Intramural Res Support P NCI, Chemoprevent Lab, Bethesda, MD 20814 USA NCI Bethesda MD USA 20814NCI, Chemoprevent Lab, Bethesda, MD 20814 USA Natl Hlth Res Inst, Div Mol & Genom Med, Taipei, Taiwan Natl Hlth Res Inst Taipei Taiwan t, Div Mol & Genom Med, Taipei, Taiwan NCI,erick,rick Canc Res & Dev Ctr, Div Basic Sci, Lab Biochem Physiol, Fred NCI Frederick MD USA 21702 Ctr, Div Basic Sci, Lab Biochem Physiol, Fred Bar Ilan Univ, Interdisciplinary Dept, IL-52900 Ramat Gan, Israel Bar IlanUniv Ramat Gan Israel IL-52900 Dept, IL-52900 Ramat Gan, Israel Univ Hong Kong, Inst Mol Biol, Pokfulam, Hong Kong Univ Hong Kong Pokfulam Hong Kong g, Inst Mol Biol, Pokfulam, Hong Kong
Titolo Testata:
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
fascicolo: 2, volume: 258, anno: 1999,
pagine: 366 - 373
SICI:
0006-291X(19990510)258:2<366:FAOHSR>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
TGF-BETA SUPERFAMILY; NEURAL INDUCTION; SIGNAL-TRANSDUCTION; VENTRAL MESODERM; TUMOR-SUPPRESSOR; XENOPUS ECTODERM; ACTS DOWNSTREAM; IN-VIVO; RECEPTOR; PROTEINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Xu, RH NCI,rograms,ck Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support P NCI Frederick MD USA 21702 AIC Frederick, Intramural Res Support P
Citazione:
R.H. Xu et al., "Functional analysis of human Smad1: Role of the amino-terminal domain", BIOC BIOP R, 258(2), 1999, pp. 366-373

Abstract

The signals originating from transforming growth factor beta/activin/bone morphogenetic proteins (BMPs) are transduced by a set of evolutionarily conserved family of Smad proteins which, upon activation, directly translocateto the nucleus where they may activate transcription. Smad proteins of different species contain conserved amino- (N) and carboxy- (C) terminal domains separated by a proline-rich linker. Human, Drosophila, and Xenopus Smad1all have been shown to mediate the biological effects of BMP-4 in Xenopus embryos. We have investigated the functional domains of human Smad1 (hSmad1) using the Xenopus embryo system. Dorsal injection of hSmad1 RNA into the 4-cell-stage embryos results in embryonic ventralization. Since the C-terminus of Smads has been shown to mediate the transcriptional activity, whereas this activity is masked by the presence of the N-terminus, we tested the effect of a hSmad1 construct lacking the C-terminal domain [hSmad1(N)] in the Xenopus embryo system. Surprisingly, we found that hSmad1(N) not only synergizes with hSmad1 in embryonic ventralization, but induces ventralization by itself. Ectopic expression of a dominant negative BMP receptor (DN-BR)as well as neural inducers noggin and chordin induce neurogenesis in the animal cap, which is inhibited by co-expression of either hSmad1 or hSmad1(N). Ventral expression of DN-BR induces formation of a second body axis at tailbud stage, which is also prevented by hSmad1 and hSmad1(N). It has recently been reported that calmodulin interacts with the N-terminal domain of Smad proteins. We demonstrate that the ventralizing activity of hSmad1 and hSmad1(N) is markedly inhibited by calmodulin. Thus, calmodulin acts as a Smad1 inhibitor. A model is proposed to accomodate these findings. (C) 1999 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 01:12:34