Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

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...
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Feeding intelligence: comparative evaluation of ChatGPT and clinical guidelines for nutritional management in head and neck cancer.

Journal of translational medicine·2025
Same author

DOT1L regulates dystrophin expression and is critical for cardiac function.

Genes & development·2011
Same author

The ribosomal intergenic spacer (IGS) region in Schistosoma japonicum: structure and comparisons with related species.

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases·2011
Same author

Effects of intravesical liposome-mediated human beta-defensin-2 gene transfection in a mouse urinary tract infection model.

Microbiology and immunology·2011
Same author

A polyacrylamide microbead-integrated chip for the large-scale manufacture of ready-to-use esiRNA.

Lab on a chip·2011
Same author

Investigation on wide-band scattering of a 2-D target above 1-D randomly rough surface by FDTD method.

Optics express·2011

Related Experiment Video

Updated: Jul 8, 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

Dismantling the TGF-β Axis: A Critical Transition from Occupancy-based Kinase Inhibitors to Event-driven Degraders.

Shasha Shen1, Juan Li1, Xue Cui1

  • 1Department of Head and Neck Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Mini Reviews in Medicinal Chemistry
|July 7, 2026
PubMed
Summary

Targeted protein degradation (TPD) offers a novel approach to inhibiting the transforming growth factor beta (TGF-β) pathway, overcoming limitations of traditional inhibitors. This strategy promises more potent, selective, and safer cancer therapeutics.

Keywords:
E3 ligasePROTACsTGF-β signalingkinase inhibitorsmedicinal chemistrymolecular gluesprecision oncology

More Related Videos

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
07:05

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing

Published on: February 26, 2021

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Related Experiment Videos

Last Updated: Jul 8, 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

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
07:05

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing

Published on: February 26, 2021

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Molecular Biology

Background:

  • The transforming growth factor beta (TGF-β) signaling pathway exhibits a dual role in cancer, promoting tumor suppression in early stages but driving metastasis and immune evasion in advanced disease.
  • Conventional TGF-β inhibitors, mainly ATP-competitive kinase blockers, have encountered significant clinical challenges, including dose-limiting toxicities and the emergence of resistance mechanisms.
  • Targeted Protein Degradation (TPD) represents a paradigm shift from occupancy-based inhibition to event-driven degradation of target proteins.

Purpose of the Study:

  • To provide a medicinal chemistry perspective on the evolution of TGF-β modulators from traditional inhibitors to TPD-based strategies.
  • To analyze the chemical optimization of TGF-β modulators, focusing on enhancing ternary complex stability and catalytic efficiency.
  • To explore the role of artificial intelligence (AI) and molecular docking in designing next-generation bifunctional degraders like PROTACs and LYTACs.

Main Methods:

  • Systematic analysis of the chemical evolution of TGF-β modulators.
  • Review of structure-activity relationship (SAR) optimizations, including linker rigidification and E3 ligase selection.
  • Discussion of AI and molecular docking applications in designing bifunctional degraders.

Main Results:

  • Rational SAR optimization, including linker rigidification and tissue-specific E3 ligase selection, improves ternary complex stability and catalytic efficiency (DC50).
  • AI and molecular docking are instrumental in guiding the design of advanced bifunctional degraders (PROTACs, LYTACs).
  • The transition to TPD offers a promising avenue for overcoming the limitations of traditional TGF-β inhibitors.

Conclusions:

  • TPD strategies provide a roadmap for effectively dismantling the TGF-β signaling axis in cancer.
  • Next-generation bifunctional degraders designed using AI and advanced chemistry hold potential for developing more potent, selective, and safer TGF-β-targeted therapies.
  • This review synthesizes current research to guide future therapeutic development against TGF-β-driven cancers.