Related Experiment Video

Updated: May 24, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Key role for ubiquitin protein modification in TGFβ signal transduction

Miriam De Boeck1, Peter ten Dijke

  • 1Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands. M.de_Boeck@lumc.nl

Upsala Journal of Medical Sciences
|February 17, 2012
PubMed

Insights

Ubiquitin modifications regulate transforming growth factor beta (TGFβ) signaling. E3 ligases and deubiquitinating enzymes control TGFβ pathway components, impacting cell behavior and disease.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • Transforming growth factor beta (TGFβ) superfamily regulates cell behavior via Smad and non-Smad pathways.
  • Dysregulation of TGFβ signaling is linked to tumorigenesis.
  • Ubiquitination by E3 ligases targets key TGFβ pathway components for degradation.

Purpose of the Study:

  • To provide an overview of the known players in ubiquitin modification of TGFβ signaling.
  • To focus on recent advances in understanding the role of E3 ligases and deubiquitinating enzymes.
  • To highlight how ubiquitin modifications mediate signaling cross-talk.

Main Methods:

  • Review of existing literature on TGFβ signaling and ubiquitination.
  • Analysis of the roles of specific E3 ligases (e.g., Smurfs, Arkadia) and adaptor proteins.
  • Examination of the impact of deubiquitinating enzymes (DUBs) and non-degradative ubiquitin modifications.

Main Results:

  • E3 ligases like Smurfs act as negative regulators, while others like Arkadia enhance TGFβ signaling by degrading repressors.
  • E3 ligases mediate cross-talk between multiple signaling pathways.
  • Ubiquitination and deubiquitination are critical for controlling TGFβ pathway activity.

Conclusions:

  • Ubiquitin modifications are central to TGFβ signal transduction.
  • A complex network of E3 ligases, adaptors, and DUBs tightly regulates the TGFβ pathway.
  • Understanding these modifications offers insights into TGFβ-related diseases and potential therapeutic targets.

More Related Videos

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model09:00

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...