Related Experiment Video

Updated: Oct 18, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by

J S Hardwick1, F G Kuruvilla, J K Tong

  • 1Howard Hughes Medical Institute, Harvard Center for Genomics Research, Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 28, 1999
PubMed

Insights

Rapamycin inhibits Target of Rapamycin (Tor) proteins, impacting nutrient-sensitive pathways in yeast. This study reveals Tor proteins directly regulate glucose and nitrogen signaling, affecting glycolysis and the citric acid cycle.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Yeast Genetics

Background:

  • The immunosuppressant rapamycin targets Tor proteins (Tor1p and Tor2p), inducing nutrient deprivation responses via translational arrest.
  • Understanding the direct impact of Tor proteins on nutrient-sensitive pathways is crucial for deciphering cellular regulation.

Purpose of the Study:

  • To investigate the immediate transcriptional response of yeast to rapamycin treatment.
  • To determine the direct effects of Tor proteins on nutrient-sensitive signaling pathways, including glucose and nitrogen metabolism.

Main Methods:

  • Yeast grown in rich media were treated with rapamycin.
  • Transcriptional responses were measured to assess pathway modulation.
  • Genome-based and biochemical approaches were employed.

Main Results:

  • Tor proteins directly modulate glucose activation and nitrogen discrimination pathways.
  • Pathways responding to the diauxic shift, such as glycolysis and the citric acid cycle, are directly affected by Tor proteins.
  • Tor proteins do not directly modulate general amino acid control, nitrogen starvation, or sporulation pathways.
  • Rapamycin treatment increased the electrophoretic mobility of the Ure2p-Gln3p complex.

Conclusions:

  • Tor proteins play a direct role in sensing and responding to nutrient availability, particularly glucose and nitrogen levels.
  • The study delineates a cellular pathway modulated by rapamycin's target, the Tor proteins.
  • Integrated genomic and biochemical methods effectively mapped cellular responses to small molecule inhibition.

More Related Videos

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

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...
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
Transcriptional Regulation: Riboswitches01:23

Transcriptional Regulation: Riboswitches

Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...