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Updated: May 5, 2026

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The Smad7-Skp2 complex orchestrates Myc stability, impacting on the cytostatic effect of TGF-β

Tae-Aug Kim1, Jin Muk Kang, Ja-Shil Hyun

  • 1CHA Cancer Institute, CHA University, Seoul 135-081, Korea.

Journal of Cell Science
|November 22, 2013
PubMed

Insights

Smad7 targets Myc oncoprotein for degradation, inhibiting cancer cell growth. This discovery offers a potential new therapeutic strategy for cancer treatment by stabilizing Myc.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • The Myc proto-oncogene is frequently activated in human cancers, driving tumorigenesis.
  • Dysregulated Myc oncoprotein contributes to cancer development across various tissues.
  • Targeting Myc stability is a promising strategy for cancer therapy.

Purpose of the Study:

  • To investigate the role of Smad7 in regulating Myc stability and activity.
  • To explore Smad7 as a potential therapeutic target for cancer treatment.

Main Methods:

  • Investigated Smad7's effect on Myc protein levels and transcriptional activity.
  • Examined Smad7's interaction with Myc and Skp2 (an F-box protein).
  • Assessed the impact of Smad7 on Myc ubiquitylation and cancer cell proliferation.

Main Results:

  • Ectopic Smad7 expression downregulated Myc protein levels without affecting transcription.
  • Smad7 repressed Myc transcriptional activity, inhibiting cell proliferation and tumorigenesis.
  • Smad7 enhanced Myc ubiquitylation by recruiting Skp2, leading to Myc degradation.
  • Ablation of Smad7 reduced sensitivity to TGF-β's growth inhibitory effects due to stable Myc.

Conclusions:

  • Smad7 plays a critical role in the degradation of Myc oncoprotein.
  • Smad7 enhances the cytostatic effects of TGF-β signaling.
  • Smad7 represents a potential novel therapeutic target for cancer treatment.
Keywords:
MycProtein stabilitySkp2Smad7Ubiquitylation

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