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Related Concept Videos

The Ras Gene02:38

The Ras Gene

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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...
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MAPK Signaling Cascades01:07

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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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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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The JAK-STAT Signaling Pathway01:20

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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...
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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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...
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Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
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Ras signaling through RASSF proteins.

Howard Donninger1, M Lee Schmidt2, Jessica Mezzanotte3

  • 1Department of Medicine, University of Louisville, KY, 40202, USA.

Seminars in Cell & Developmental Biology
|June 12, 2016
PubMed
Summary
This summary is machine-generated.

The Ras association domain family (RASSF) proteins act as scaffolds, linking Ras signaling to diverse cellular processes including apoptosis, senescence, and DNA repair. Epigenetic silencing of RASSF genes in tumors promotes cancer progression.

Keywords:
ApoptosisNORE1ARASSF1ARasSignalingp53

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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • The Ras signaling pathway is crucial for cell growth and survival.
  • Ras association domain family (RASSF) proteins are emerging as key regulators of Ras.
  • RASSF proteins lack enzymatic activity and function as scaffolds, connecting Ras to various cellular pathways.

Purpose of the Study:

  • To elucidate the diverse roles of RASSF proteins in cellular signaling.
  • To investigate the impact of RASSF proteins on pathways beyond apoptosis.
  • To understand the implications of RASSF gene inactivation in human cancers.

Main Methods:

  • Bioinformatic analysis of RASSF protein domains.
  • Experimental investigation of RASSF protein interactions with signaling molecules.
  • Analysis of RASSF gene expression and epigenetic modifications in tumor samples.

Main Results:

  • RASSF proteins link Ras to apoptosis, senescence, inflammation, autophagy, DNA repair, and protein acetylation.
  • RASSF proteins can influence pro-mitogenic Ras effector pathways like Raf.
  • Epigenetic inactivation of RASSF genes in tumors disconnects Ras from pro-death signaling, promoting transformation and metastasis.

Conclusions:

  • RASSF proteins are versatile regulators of Ras signaling with broad cellular functions.
  • RASSF proteins play a critical role in tumor suppression by mediating pro-apoptotic and anti-proliferative signals.
  • Targeting RASSF epigenetic silencing may offer therapeutic strategies for cancer treatment.