Related Experiment Video

Updated: Jun 17, 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

Geldanamycin inhibits TGF-beta signaling through induction of Hsp70

Chang-Hyun Yun1, Sun-Young Yoon, Thuy Trang Nguyen

  • 1Lee Gi Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo, Yeonsu, Incheon 406-840, Republic of Korea.

Archives of Biochemistry and Biophysics
|December 10, 2009
PubMed

Insights

Geldanamycin inhibits transforming growth factor-beta (TGF-beta) signaling by inducing Hsp70, which then interacts with TGF-beta receptors, leading to their degradation. This mechanism offers potential therapeutic strategies for TGF-beta-related diseases like cancer.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Transforming growth factor-beta (TGF-beta) signaling pathway dysregulation is linked to various diseases, including cancer.
  • Targeting the TGF-beta pathway with pharmacological inhibitors presents a promising therapeutic approach.

Purpose of the Study:

  • To elucidate the mechanism by which the Hsp90 inhibitor geldanamycin (GA) inhibits TGF-beta signaling.
  • To investigate the role of Heat Shock Protein 70 (Hsp70) in GA-mediated TGF-beta pathway suppression.

Main Methods:

  • Western blot analysis to assess protein degradation and phosphorylation.
  • Use of Hsp70 siRNA and KNK437 to inhibit Hsp70 synthesis.
  • Investigating protein-protein interactions between Hsp70 and TGF-beta receptors.

Main Results:

  • Geldanamycin suppressed TGF-beta signaling, including Smad3 phosphorylation and target gene induction.
  • GA treatment led to proteasome-dependent degradation of TGF-beta type I and type II receptors.
  • GA-induced Hsp70 expression correlated with TGF-beta signaling inhibition.
  • Hsp70 directly interacted with TGF-beta receptors post-GA treatment, and blocking Hsp70 abrogated GA's inhibitory effect.

Conclusions:

  • GA-induced Hsp70 plays a critical role in inhibiting TGF-beta signaling.
  • GA-mediated Hsp70 induction and subsequent interaction with TGF-beta receptors are key to suppressing the pathway.
  • This mechanism highlights Hsp70 as a potential mediator in targeting TGF-beta signaling for therapeutic benefit.

More Related Videos

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

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...
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...
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...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...