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Critical Reviews™ in Eukaryotic Gene Expression

ISSN for PRINT: 1045-4403

Institutional price:	$708.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2002, Volume12

78 pages

DOI: 10.1615/CritRevEukaryotGeneExpr.v12.i2

Issue price - $169.00

Complex Smad-Dependent Transcriptional Responses in Vertebrate Development and Human Disease

Leo A. van Grunsven
Laboratory of Molecular Biology (Celgen), University of Leuven; and Department of Developmental Biology (VIB7), Flanders Intel-university Institute for Biotechnology (VIB), Campus Gasthuisberg, BIdg. O&N, Herestraat 49, B-3000 Leuven, Belgium

Danny Huylebroeck
Laboratory of Molecular Biology (Celgen), University of Leuven; and Department of Developmental Biology (VIB7), Flanders Intel-university Institute for Biotechnology (VIB), Campus Gasthuisberg, BIdg. O&N, Herestraat 49, B-3000 Leuven, Belgium

Kristin Verschueren
Laboratory of Molecular Biology (Celgen), University of Leuven; and Department of Developmental Biology (VIB7), Flanders Intel-university Institute for Biotechnology (VIB), Campus Gasthuisberg, BIdg. O&N, Herestraat 49, B-3000 Leuven, Belgium

ABSTRACT

Smad proteins mediate genomic responses to polypeptides of the transforming growth factor type b (TGF-b) family, affecting cellular proliferation and differentiation, adhesion, and death. Members of one class of these Smad proteins, the receptor-regulated Smads or R-Smads, accumulate in the nucleus on their activation byligand-bound complexes of serine-threonine kinase receptors at the cell surface. These effector proteins then participate directly in the regulation of gene expression by binding to DNA, interacting with transcription factors, and recruiting corepressors or coactivators to specific promoters. Although many nuclear Smad-interacting factors were isolated during the last 3 years, the field has recently taken a step beyond the characterization of the activity of these Smad-containing complexes on gene expression in vitro, as it addresses now their contribution to many processes in vivo. We have selected examples of such recent progress to illustrate the remarkable variation in the molecular mechanisms underlying Smad-dependent signaling depending on the non-Smad partner in the nucleus and their relevance to normal embryogenesis and consequences of their deregulation in human disorders and pathology.