Related Experiment Video

Updated: Sep 27, 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

Activation of transforming growth factor-beta signaling by SUMO-1 modification of tumor suppressor Smad4/DPC4

Xia Lin1, Min Liang, Yao-Yun Liang

  • 1Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.

The Journal of Biological Chemistry
|March 7, 2003
PubMed

Insights

Small ubiquitin-like modifier-1 (SUMO-1) conjugation regulates Smad4 activity. Sumoylation enhances transforming growth factor-beta (TGF-beta)-induced cellular responses, identifying a novel regulatory mechanism for Smad4.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Smads are key intracellular mediators in transforming growth factor-beta (TGF-beta) superfamily signaling.
  • Activated Smads complex with Smad4 and translocate to the nucleus.
  • Factors regulating Smad4 activity are largely unknown.

Purpose of the Study:

  • To investigate the role of small ubiquitin-like modifier-1 (SUMO-1) conjugation in modulating Smad4 function.
  • To identify the mechanism by which Smad4 activity is regulated.

Main Methods:

  • Investigated the physical interaction between Smad4 and Ubc9 (E2 conjugating enzyme).
  • Assessed Smad4 modification by SUMO-1 in cultured cells.
  • Identified sumoylation sites (Lys-113 and Lys-159) within the Smad4 MH1 domain.
  • Utilized site-directed mutagenesis to evaluate the impact of sumoylation on Smad4 complex formation and transcriptional activity.

Main Results:

  • Smad4 physically associates with Ubc9, the key enzyme in sumoylation.
  • Smad4 undergoes SUMO-1 modification at endogenous levels.
  • Mutations at Lys-113 and Lys-159 did not impair Smad4 complex formation with Smad2 and FAST on the Mix.2 promoter.
  • Overexpression of SUMO-1 potentiated TGF-beta-induced transcriptional responses.

Conclusions:

  • Sumoylation is a novel mechanism regulating Smad4 activity.
  • SUMO-1 conjugation enhances Smad4-dependent growth inhibitory and transcriptional responses.
  • This study elucidates a new pathway for controlling TGF-beta signaling via Smad4 modification.

More Related Videos

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...