Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

5.1K
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...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

3.6K
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...
3.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.5K
1.5K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.2K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.2K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

7.3K
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...
7.3K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

9.1K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Metabolic signatures in sciatic nerve of PMP22 transgenic rats provide insights into the pathogenesis of charcot-marie-tooth disease type 1 A.

Scientific reports·2026
Same author

Skeletal Muscle Biomarkers of Amyotrophic Lateral Sclerosis: A Large-Scale, Multi-Cohort Proteomic Study.

Annals of neurology·2025
Same author

Skeletal muscle biomarkers of amyotrophic lateral sclerosis: a large-scale, multi-cohort proteomic study.

medRxiv : the preprint server for health sciences·2025
Same author

Integrative Proteogenomics for Differential Expression and Splicing Variation in a DM1 Mouse Model.

Molecular & cellular proteomics : MCP·2023
Same author

Clinical re-biopsy of segmental gains-the primary source of preimplantation genetic testing false positives.

Journal of assisted reproduction and genetics·2022
Same author

STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia.

iScience·2021
Same journal

The Outcome of Cardiac Hydatid Surgery in The Iraqi Center of Heart Diseases.

F1000Research·2026
Same journal

Perception of body donation among the Phase-1 medical students, a questionnaire-based study.

F1000Research·2026
Same journal

Exploring Infertility in Saudi Arabia: Qualitative Insights into IVF Treatment Services and Policy Recommendations.

F1000Research·2026
Same journal

Cyber Military Operations under International Humanitarian Law: Interpreting the Concept of "Attack" and Challenges in Protecting Civilians.

F1000Research·2026
Same journal

Sentiment Analysis of Acceptance TVET Online Courses on the Skill Academy App from Google Play: Leveraging Text Mining with Comparison Machine Learning Model.

F1000Research·2026
Same journal

Emotional intelligence: An important skill to learn now more than ever.

F1000Research·2026
See all related articles

Related Experiment Video

Updated: May 4, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

2.5K

Rapamycin-insensitive mTORC1 activity controls eIF4E:4E-BP1 binding.

Mark Livingstone1, Michael Bidinosti2

  • 1Biochemistry and McGill Cancer Centre, McGill University, Montreal, Canada ; Cytokine Signalling Unit, Institut Pasteur, Paris, France.

F1000Research
|December 24, 2013
PubMed
Summary
This summary is machine-generated.

The mammalian target of rapamycin (mTOR) pathway

More Related Videos

Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions
10:40

Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions

Published on: December 28, 2016

7.3K
Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

856

Related Experiment Videos

Last Updated: May 4, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

2.5K
Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions
10:40

Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions

Published on: December 28, 2016

7.3K
Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

856

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Mammalian target of rapamycin (mTOR) signaling is crucial for cell growth and metabolism.
  • mTOR exists in two complexes, mTORC1 and mTORC2, with distinct sensitivities to rapamycin.
  • Phosphorylation of 4E-binding protein 1 (4E-BP1) by mTOR regulates protein synthesis initiation.

Purpose of the Study:

  • To clarify the role of specific 4E-BP1 phosphorylation sites in regulating eIF4E binding.
  • To differentiate the mechanisms of rapamycin and mTOR kinase domain inhibitors.

Main Methods:

  • Utilized serine (Ser)-to-alanine (Ala) and threonine (Thr)-to-Ala phosphorylation site mutants of 4E-BP1.
  • Assessed the impact of these mutations on the binding of 4E-BP1 to eukaryotic initiation factor 4E (eIF4E).

Main Results:

  • Demonstrated that rapamycin-insensitive phosphorylation of 4E-BP1 at threonine 46 (Thr46) is sufficient to block eIF4E binding.
  • Identified Thr46 phosphorylation as a key event in inhibiting cap-dependent translation initiation.

Conclusions:

  • The initial, rapamycin-insensitive phosphorylation of 4E-BP1 at Thr46 is critical for preventing eIF4E:4E-BP1 complex formation.
  • This finding distinguishes the action of second-generation mTOR kinase domain inhibitors from rapamycin analogues, impacting drug development.