LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control.

Animals CRISPR-Cas Systems Colonic Neoplasms / genetics Female Gene Editing Gene Expression Regulation, Developmental HCT116 Cells HEK293 Cells HeLa Cells Heterografts Hippo Signaling Pathway Humans Liver / abnormalities MCF-7 Cells Mechanistic Target of Rapamycin Complex 1 / genetics Mice Mice, Nude Mice, Transgenic Myocardium / metabolism Neurofibromin 2 / deficiency Organ Size Protein Serine-Threonine Kinases / deficiency Ras Homolog Enriched in Brain Protein / genetics Regulatory-Associated Protein of mTOR / genetics Signal Transduction Tumor Suppressor Proteins / deficiency

Journal

Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575

Informations de publication

Date de publication:
02 2020
Historique:
received: 08 11 2019
accepted: 06 01 2020
pubmed: 6 2 2020
medline: 16 4 2020
entrez: 5 2 2020
Statut: ppublish

Résumé

The Hippo and mammalian target of rapamycin complex 1 (mTORC1) pathways are the two predominant growth-control pathways that dictate proper organ development. We therefore explored potential crosstalk between these two functionally relevant pathways to coordinate their growth-control functions. We found that the LATS1 and LATS2 kinases, the core components of the Hippo pathway, phosphorylate S606 of Raptor, an essential component of mTORC1, to attenuate mTORC1 activation by impairing the interaction of Raptor with Rheb. The phosphomimetic Raptor-S606D knock-in mutant led to a reduction in cell size and proliferation. Compared with Raptor

Identifiants

DOI: 10.1038/s41556-020-0463-6 PMID: 32015438 PMC: PMC7076906
pubmed: 32015438
doi: 10.1038/s41556-020-0463-6
pii: 10.1038/s41556-020-0463-6
pmc: PMC7076906
mid: NIHMS1548339
doi:

Substances chimiques

Neurofibromin 2 0
Ras Homolog Enriched in Brain Protein 0
Regulatory-Associated Protein of mTOR 0
Rheb protein, mouse 0
Rptor protein, mouse 0
Tumor Suppressor Proteins 0
Lats1 protein, mouse EC 2.7.1.-
LATS2 protein, mouse EC 2.7.11.1
Mechanistic Target of Rapamycin Complex 1 EC 2.7.11.1
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

246-256

Subventions

Organisme : NCI NIH HHS
ID : R01 CA200651
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK123704
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA181342
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM094777
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM130457
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY012196
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA207867
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA222571
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM117150
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA120964
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA200573
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA177910
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090255
Pays : United States

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Auteurs

Wenjian Gan (W)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. ganw@musc.edu.
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA. ganw@musc.edu.
ORCID: 0000-0001-7599-5020

Xiaoming Dai (X)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Xiangpeng Dai (X)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Jun Xie (J)

Li Weibo Institute for Rare Diseases Research and Horae Gene Therapy Center and Vector Core, University of Massachusetts Medical School, Worcester, MA, USA.
ORCID: 0000-0001-9565-1567

Shasha Yin (S)

Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.

Junjie Zhu (J)

F.M. Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA.

Chen Wang (C)

F.M. Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA.

Yuchen Liu (Y)

Department of Developmental Biology, Harvard Stem Cell Institute, Harvard School of Dental Medicine, Boston, MA, USA.
ORCID: 0000-0001-8922-9976

Jianping Guo (J)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Min Wang (M)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Departments of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Jing Liu (J)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Jia Hu (J)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Departments of Urology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ryan J Quinton (RJ)

The Laboratory of Cancer Cell Biology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Division of Hematology and Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

Neil J Ganem (NJ)

The Laboratory of Cancer Cell Biology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Division of Hematology and Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

Pengda Liu (P)

Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

John M Asara (JM)

Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA, USA.

Pier Paolo Pandolfi (PP)

Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-5352-5295

Yingzi Yang (Y)

Department of Developmental Biology, Harvard Stem Cell Institute, Harvard School of Dental Medicine, Boston, MA, USA.
ORCID: 0000-0003-3933-887X

Zhigang He (Z)

F.M. Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-6080-6880

Guangping Gao (G)

Li Weibo Institute for Rare Diseases Research and Horae Gene Therapy Center and Vector Core, University of Massachusetts Medical School, Worcester, MA, USA.
ORCID: 0000-0003-0097-9012

Wenyi Wei (W)

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. wwei2@bidmc.harvard.edu.
ORCID: 0000-0003-0512-3811

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Tumeurs de l'intestin › Tumeurs du côlon › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes au cours du développement › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cellules HCT116 › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Cellules › Cellules épithéliales › Cellules HEK293 › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Cellules › Cellules épithéliales › Cellules HeLa › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Régions du corps › Transplants › Hétérogreffes › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Hippo › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Système digestif › Foie › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Cellules › Cellules cultivées › Lignée cellulaire › Cellules MCF-7 › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Complexe-1 cible mécanistique de la rapamycine › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris nude › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Tissus › Muscles › Muscle strié › Myocarde › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Neurofibromine-2 › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Phénomènes physiologiques › Croissance et développement › Croissance › Taille d'organe › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Neuropeptides › Protéine homologue de Ras enrichie dans le cerveau › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Complexe-1 cible mécanistique de la rapamycine › Protéine de régulation associée à mTOR › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Transduction du signal › LATS suppresses mTORC1 activity to directly...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › LATS suppresses mTORC1 activity to directly...