Evidence map›Paper›PMID 26972053›Full record

ArticleCell2016

The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway.

Lynne Chantranupong, Sonia M Scaria, Robert A Saxton, Melanie P Gygi, Kuang Shen, Gregory A Wyant, Tim Wang, J Wade Harper, Steven P Gygi, David M Sabatini

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 505 papers.

0numbers the graph read from it
0cells of the map it votes in
505citing papers in PubMed
41.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

505 citing papers in PubMed, 779 citations in OpenAlex.

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445 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Lynne ChantranupongDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA.
Sonia M ScariaDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA.
Robert A SaxtonDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA.
Melanie P GygiDepartment of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Kuang ShenDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA.
Gregory A WyantDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA.
Tim WangDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA.
J Wade HarperDepartment of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
David M SabatiniDepartment of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA. Electronic address: sabatini@wi.mit.edu.
Broad Institute · USHarvard University · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Andreea O'Connell · 1985 to 2026
$93.9M
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Regulation of the mTOR Pathway By NutrientsR01CA103866 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2004 to 2021
$7.0M
Systematic Exploration of the Human InteractomeU41HG006673 · NHGRI · HARVARD MEDICAL SCHOOL · PI GYGI, STEVEN P, HARPER, JEFFREY W · 2012 to 2017
$5.5M
TRANSLATIONAL CONTROL BY RAPAMYCIN-SENSITIVE SIGNALINGR01AI047389 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2000 to 2021
$4.9M
Novel Components of the mTORC1 and mTORC2 PathwaysR37AI047389 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI SABATINI, DAVID M. · 2010 to 2019
$4.8M
Network organization of the human autophagy systemR01GM095567 · NIGMS · HARVARD MEDICAL SCHOOL · PI HARPER, JEFFREY W, KIMMELMAN, ALEC · 2011 to 2018
$3.0M
Characterization of MWS/DEN, a novel regulator of amino acid signaling to mTORC1F31CA180271 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CHANTRANUPONG, LYNNE · 2013 to 2015
$128k
Improving targeted therapies through functional genomic approachesF31CA189437 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WANG, TIM · 2014 to 2017
$107k
NCI NIH HHS F31 CA180271NCI NIH HHS F31 CA189437NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA103866NCI NIH HHS R01CA103866NHGRI NIH HHS U41 HG006673NIAID NIH HHS AI47389)NIAID NIH HHS R01 AI047389NIAID NIH HHS R37 AI047389NIGMS NIH HHS R01 GM095567NIGMS NIH HHS T32 GM007287
6 · The paper itself

Abstract

Amino acids signal to the mTOR complex I (mTORC1) growth pathway through the Rag GTPases. Multiple distinct complexes regulate the Rags, including GATOR1, a GTPase activating protein (GAP), and GATOR2, a positive regulator of unknown molecular function. Arginine stimulation of cells activates mTORC1, but how it is sensed is not well understood. Recently, SLC38A9 was identified as a putative lysosomal arginine sensor required for arginine to activate mTORC1 but how arginine deprivation represses mTORC1 is unknown. Here, we show that CASTOR1, a previously uncharacterized protein, interacts with GATOR2 and is required for arginine deprivation to inhibit mTORC1. CASTOR1 homodimerizes and can also heterodimerize with the related protein, CASTOR2. Arginine disrupts the CASTOR1-GATOR2 complex by binding to CASTOR1 with a dissociation constant of ~30 μM, and its arginine-binding capacity is required for arginine to activate mTORC1 in cells. Collectively, these results establish CASTOR1 as an arginine sensor for the mTORC1 pathway.

Indexed as

ArginineCarrier ProteinsHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesProtein MultimerizationTOR Serine-Threonine KinasesArginineCarrier ProteinsCASTOR1 protein, humanCASTOR2 protein, humanIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesTOR Serine-Threonine Kinases

Identifiers

PMID26972053
PMCPMC4808398
OpenAlexW2293646973

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.