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Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Retinoblastoma Gene01:20

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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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...
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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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...

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Updated: May 8, 2026

Live-imaging of Breast Epithelial Cell Migration After the Transient Depletion of TIP60
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RGS6 suppresses Ras-induced cellular transformation by facilitating Tip60-mediated Dnmt1 degradation and promoting

J Huang1, A Stewart1, B Maity1

  • 1Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Oncogene
|September 3, 2013
PubMed
Summary

Regulator of G protein signaling 6 (RGS6) suppresses Ras-induced cancer by promoting degradation of DNA methyltransferase 1 (Dnmt1), inhibiting cell proliferation and promoting apoptosis. RGS6 acts as a scaffold for Dnmt1 and Tip60, facilitating Dnmt1 breakdown and blocking oncogenic transformation.

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Inducible and Reversible Dominant-negative (DN) Protein Inhibition
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10:27

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08:35

Inducible and Reversible Dominant-negative (DN) Protein Inhibition

Published on: January 7, 2019

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • RAS proto-oncogene mutations drive cancer by promoting cell proliferation.
  • DNA methyltransferase 1 (Dnmt1) silences tumor suppressors, aiding Ras-driven transformation and is overexpressed in cancers.

Purpose of the Study:

  • To investigate the role of Regulator of G protein signaling 6 (RGS6) in suppressing Ras-induced cellular transformation.
  • To elucidate the mechanism by which RGS6 regulates Dnmt1 expression and function.

Main Methods:

  • Utilized mouse embryonic fibroblasts from wild-type and RGS6 knockout mice.
  • Analyzed protein expression, degradation, and interactions using biochemical assays.
  • Investigated the role of RGS6 as a scaffolding protein in the Dnmt1-Tip60 complex.

Main Results:

  • Oncogenic Ras upregulated RGS6, which blocked Ras-induced cellular transformation.
  • RGS6 facilitated Tip60-mediated acetylation, ubiquitylation, and degradation of Dnmt1.
  • RGS6 scaffolding activity was essential for Dnmt1 downregulation and inhibition of its anti-apoptotic function.

Conclusions:

  • RGS6 acts as a novel tumor suppressor by targeting Dnmt1 for degradation, thereby counteracting Ras-induced oncogenic transformation.
  • RGS6's RGS domain mediates interaction with Tip60, crucial for Dnmt1 regulation.
  • RGS6 represents a potential therapeutic target for cancers driven by Ras and characterized by Dnmt1 overexpression.