The rapid induction of alpha interferon (IFN-alpha) and IFN-beta expression plays a critical role in the innate immune response against viral infection. We studied the effects of transforming growth factor beta (TGF-beta) and its intracellular effectors, the Smads, on the function of IRF-7, an essential transcription factor for IFN-alpha and -beta induction. IRF-7 interacted with Smads, and IRF...

Transforming growth factors (TGFs)are multipotent in their biologic activity, regulating cell growth and differentiation as well as extracellular matrix deposition and degradation. Most of these activities involve modulation of gene transcription, but TGF1 has been shown previously to substantially increase the expression of elastin by stabilization of tropoelastin mRNA through a signaling path...

Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 wer...

Sip1 is a member of the family of two-handed zinc finger/ homeodomain proteins identified as a DNA binding transcriptional repressor interacting with receptor-activated SMADs. SMADs are intracellular signal transducers activated by binding of TGFb/BMP ligands to their receptors and are involved in the control of cellular functions of embryonic development and tissue homeostasis. During mouse an...

Planarians represent an excellent model to study the processes of body axis and organ re-specification during regeneration. Previous studies have revealed a conserved role for the bone morphogenetic protein (BMP) pathway and its intracellular mediators Smad1/5/8 and Smad4 in planarian dorsoventral (DV) axis re-establishment. In an attempt to gain further insight into the role of this signalling...

BACKGROUND Bone morphogenetic proteins (BMPs) are multifunctional proteins that regulate the proliferation, differentiation, and migration of a large variety of cell types. Like other members of the transforming growth factor-beta family, BMPs elicit their cellular effects through activating specific combinations of type I and type II serine/threonine kinase receptors and their downstream effec...

The transforming growth factor (TGF)-beta superfamily regulates cell proliferation, apoptosis, differentiation, migration, and development. Canonical TGFbeta signals are transduced to the nucleus via Smads in both major signaling branches, bone morphogenetic protein (BMP) or Activin/Nodal/TGFbeta. Smurf ubiquitin (Ub) ligases attenuate these pathways by targeting Smads and other signaling compo...

.............................................................................................................9 INTRODUCTION ..................................................................................................10 1 Regulation of transcription in eukaryotes ......................................................10 1.1 Recruitment of co-activators and co-repressors .......................

Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of ...

Epithelial to mesenchymal transition (EMT) occurs during development and cancer progression to metastasis and results in enhanced cell motility and invasion. Transforming growth factor-beta (TGF-beta) induces EMT through Smads, leading to transcriptional regulation, and through non-Smad pathways. We observe that TGF-beta induces increased cell size and protein content during EMT. This translati...