Evidence map›Paper›PMID 25418727›Full record

ArticleStem cell reports2014

Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors.

Dongjun Lee, Stephen M Sykes, Demetrios Kalaitzidis, Andrew A Lane, Youmna Kfoury, Marc H G P Raaijmakers, Ying-Hua Wang, Scott A Armstrong, David T Scadden

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

Article in Stem cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Dongjun LeeCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Stephen M SykesCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Demetrios KalaitzidisCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Andrew A LaneCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Youmna KfouryCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Marc H G P RaaijmakersDepartment of Hematology and Erasmus Stem Cell Institute, Erasmus University Medical Center, 3015GE Rotterdam, the Netherlands.
Ying-Hua WangCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Scott A ArmstrongDepartment of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
David T ScaddenCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: david_scadden@harvard.edu.
Harvard Stem Cell Institute · USHarvard University · USErasmus MC · NLMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · US

Funding

Microenvironmental control of progenitors in organ dysfunction and repairU01HL100402 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI KIM, CARLA F., SCADDEN, DAVID T · 2009 to 2015
$8.5M
MECHANISMS OF HEMATOPOIESIS IN AIDSR01HL044851 · NHLBI · NEW ENGLAND DEACONESS HOSPITAL · PI SCADDEN, DAVID T · 1991 to 2015
$7.7M
FUNCTIONAL ISOLATION OF HUMAN HEMATOPOIETIC STEM CELLSR01DK050234 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI SCADDEN, DAVID T · 1995 to 2012
$3.7M
Stem Cell Engagement of the NicheR01HL097794 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SCADDEN, DAVID T · 2009 to 2012
$2.4M
Foxo transcription factors are required for maintenance of acute myeloid leukemiaR00CA158461 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI SYKES, STEPHEN MATTHEW · 2012 to 2014
$641k
mTOR Complexes in HematopoiesisK01DK092300 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KALAITZIDIS, DEMETRIOS · 2011 to 2015
$601k
NCI NIH HHS R00 CA158461NHLBI NIH HHS HL044851NHLBI NIH HHS HL97794NHLBI NIH HHS R01 HL044851NHLBI NIH HHS R01 HL097794NHLBI NIH HHS U01 HL100402NHLBI NIH HHS U01HL100402NIDDK NIH HHS K01 DK092300NIDDK NIH HHS K01DK092300NIDDK NIH HHS R01 DK050234
6 · The paper itself

Abstract

Central to cellular proliferative, survival, and metabolic responses is the serine/threonine kinase mTOR, which is activated in many human cancers. mTOR is present in distinct complexes that are either modulated by AKT (mTORC1) or are upstream and regulatory of it (mTORC2). Governance of mTORC2 activity is poorly understood. Here, we report a transmembrane molecule in hematopoietic progenitor cells that physically interacts with and inhibits RICTOR, an essential component of mTORC2. Upstream of mTORC2 (UT2) negatively regulates mTORC2 enzymatic activity, reducing AKT(S473), PKCα, and NDRG1 phosphorylation and increasing FOXO transcriptional activity in an mTORC2-dependent manner. Modulating UT2 levels altered animal survival in a T cell acute lymphoid leukemia (T-ALL) model that is known to be mTORC2 sensitive. These studies identify an inhibitory component upstream of mTORC2 in hematopoietic cells that can reduce mortality from NOTCH-induced T-ALL. A transmembrane inhibitor of mTORC2 may provide an attractive target to affect this critical cell regulatory pathway.

Indexed as

AnimalsCarrier ProteinsCell Cycle ProteinsCells, CulturedForkhead Box Protein O3Forkhead Transcription FactorsHEK293 CellsHematopoietic Stem CellsHumansImmunoblottingIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 2Membrane Transport ProteinsMiceMice, KnockoutMice, TransgenicCarrier ProteinsCell Cycle ProteinsForkhead Box Protein O3Forkhead Transcription FactorsFoxO3 protein, mouseIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 2Membrane Transport ProteinsMultiprotein ComplexesN-myc Downstream-Regulated Gene 1 ProteinProtein Kinase C-alphaProto-Oncogene Proteins c-aktRapamycin-Insensitive Companion of mTOR ProteinReceptors, Notchrictor protein, mouseTOR Serine-Threonine Kinases

Identifiers

PMID25418727
PMCPMC4235746
OpenAlexW2133009736

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.