Related Experiment Video

Updated: Aug 16, 2026

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

Ras is involved in the negative control of autophagy through the class I PI3-kinase

Shuichi Furuta1, Eiko Hidaka, Aya Ogata

  • 1Department of Molecular Biology and Biochemistry, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan.

Oncogene
|April 6, 2004
PubMed

Insights

Oncogenic Ras proteins suppress autophagy, a cellular protein degradation process, via the PI3-kinase pathway. This Ras-mediated suppression is sensitive to mTOR inhibition and impacts cell growth control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Ras proteins are key regulators of cell proliferation, and mutations can cause cancer.
  • The role of Ras proteins in autophagy, a cellular degradation process, remains largely unknown.
  • Autophagy is crucial for controlling cell growth and survival.

Purpose of the Study:

  • To investigate the role of Ras proteins in regulating autophagy.
  • To determine the signaling pathways involved in Ras-mediated autophagy regulation.
  • To understand how Ras transformation affects nutrient deprivation-induced autophagy.

Main Methods:

  • Utilized NIH3T3 cells expressing oncogenic RasVal12.
  • Assessed long-lived protein degradation and autophagic vacuole formation.
  • Investigated the involvement of mTOR, PI3-kinase, Raf, and Ral GDS signaling pathways.
  • Examined the effects of epidermal growth factor and serum on autophagy.

Main Results:

  • Oncogenic RasVal12 transformation suppressed nutrient starvation-induced autophagy in a rapamycin-sensitive manner.
  • Ras transformation decreased autophagic vacuole formation.
  • Ras mediated the suppressive effect of growth factors on autophagy.
  • Ras-induced suppression of autophagy was dependent on class I PI3-kinase signaling.

Conclusions:

  • Ras acts as a negative regulator of autophagy during nutrient deprivation.
  • The class I PI3-kinase pathway is critical for Ras-mediated autophagy suppression.
  • These findings elucidate a novel role for Ras in cellular homeostasis and cancer development.

More Related Videos

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells09:34

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells

Published on: July 27, 2018

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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...
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...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
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...