Related Experiment Video
Updated: Aug 22, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
Itch E3 ligase-mediated regulation of TGF-beta signaling by modulating smad2 phosphorylation
Yongli Bai1, Chun Yang, Kathrin Hu
1Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Abstract:
Protein ubiquitination has been implicated in the intracellular biochemical events transduced by TGF-beta receptor via different mechanisms including the degradation of Smads or their binding proteins. Here we show that loss of Itch E3 ligase in mouse embryonic fibroblasts (MEFs) results in reduced susceptibility of TGF-beta-induced cell growth arrest and decreased phosphorylation of Smad2, without apparent alteration in protein levels for Smad2, Smad4, and Smad7 in Itch-/- MEFs. Itch promotes ubiquitination of Smad2 and augments Smad2 phosphorylation that requires an intact ligase activity of Itch. Moreover, Itch facilitates complex formation between TGF-beta receptor and Smad2 and enhances TGF-beta-induced transcription. This study reveals a previously unrecognized positive TGF-beta signaling pathway via proteolysis-independent ubiquitination.
More Related Videos
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
11:38Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
Related Concept Videos
TGF - β Signaling Pathway
The JAK-STAT Signaling Pathway
Hedgehog Signaling Pathway
PI3K/mTOR/AKT Signaling Pathway
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Regulation of Angiogenesis and Blood Supply