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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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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.
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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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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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Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Rous Sarcoma Virus (RSV) and Cancer01:03

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RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...

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Updated: Jul 4, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Constitutively active Rheb induces oncogenic transformation.

H Jiang1, P K Vogt

  • 11Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. hjiang@scripps.edu

Oncogene
|June 4, 2008
PubMed
Summary
This summary is machine-generated.

Constitutively active Rheb (Ras-homolog enriched in brain) promotes cancer by activating the PI3K-TOR pathway. Inhibiting TOR with rapamycin blocks this oncogenic transformation, highlighting TOR

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Rheb (Ras-homolog enriched in brain) is a key regulator in the PI3K-TOR signaling pathway.
  • Aberrant activation of TOR signaling is implicated in various cancers.
  • Constitutively active Rheb mutants are known to induce oncogenic transformation.

Purpose of the Study:

  • To investigate the role of Rheb in oncogenic transformation.
  • To elucidate the downstream effectors and mechanisms by which Rheb promotes cancer.
  • To determine the essentiality of TOR signaling in Rheb-mediated transformation.

Main Methods:

  • Cell culture and transformation assays using Rheb mutants.
  • Analysis of downstream TOR signaling targets (p70S6K, 4E-BP1 phosphorylation).
  • Treatment with the TOR-specific inhibitor rapamycin.
  • Mutagenesis of Rheb to alter lipid modification signals (farnesylation, myristylation).
  • Immunofluorescence microscopy for Rheb localization.

Main Results:

  • Constitutively active Rheb mutants induced oncogenic transformation, leading to larger cells with increased protein content.
  • Transformed cells exhibited constitutive phosphorylation of S6 kinase and 4E-BP1, indicating active TOR signaling.
  • Rapamycin treatment significantly inhibited Rheb-induced transformation, confirming TOR dependency.
  • Rheb-induced transformation required a C-terminal farnesylation signal for membrane localization, which could be substituted by an N-terminal myristylation signal.
  • Both wild-type and mutant Rheb localized to cytoplasmic vesicular structures, including the endoplasmic reticulum.

Conclusions:

  • TOR activity is essential for the oncogenic transformation driven by constitutively active Rheb.
  • Rheb-mediated oncogenesis is dependent on its proper cellular localization, mediated by lipid modification signals.
  • These findings identify Rheb as a critical mediator of oncogenic transformation through the PI3K-TOR pathway and suggest potential therapeutic targets.