Related Experiment Video

Updated: May 20, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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

Published on: July 17, 2019

RSK regulates activated BRAF signalling to mTORC1 and promotes melanoma growth

Yves Romeo1, Julie Moreau1, Pierre-Joachim Zindy1

  • 1Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada.

Oncogene
|July 17, 2012
PubMed

Insights

Oncogenic Ras/MAPK signaling activates mTOR and promotes protein synthesis. Inhibition of RSK (ribosomal S6 kinase) blocks tumor growth, suggesting RSK as a therapeutic target for melanoma.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The Ras/mitogen-activated protein kinase (MAPK) pathway is crucial for cell growth and survival.
  • This pathway is frequently dysregulated in cancers like melanoma due to mutations in NRAS and BRAF.
  • Hyperactive MAPK signaling enhances protein synthesis, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the mechanisms by which oncogenic Ras/MAPK signaling promotes protein synthesis.
  • To investigate the role of mammalian target of rapamycin (mTOR) and RSK (p90 ribosomal S6 kinase) in this process.
  • To evaluate RSK as a potential therapeutic target in melanoma.

Main Methods:

  • Utilized oncogenic Ras and Raf expression models.
  • Employed pharmacological inhibitors and RNA interference targeting MAPK pathway components.
  • Analyzed translation initiation complex assembly, polysome formation, and TOP mRNA translation in melanoma cell lines.
  • Assessed tumor growth in mice following RSK inhibition.

Main Results:

  • Oncogenic Ras/Raf signaling leads to constitutive activation of mTOR.
  • The MAPK-activated protein kinase RSK is partially required for these effects.
  • ERK/RSK signaling regulates translation initiation and polysome formation, particularly for TOP motif-containing mRNAs.
  • RSK inhibition effectively abrogated tumor growth in mouse models.

Conclusions:

  • RSK plays a significant role in mediating the effects of oncogenic MAPK signaling on protein synthesis and tumor growth.
  • Targeting RSK presents a promising therapeutic strategy for melanomas and other tumors with deregulated MAPK signaling.

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells06:44

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

Published on: March 1, 2024

Related Concept Videos

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...
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...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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...
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...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...