Evidence map›Paper›PMID 37846480›Full record

ArticleEMBO reports2023

The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes.

Busra Turgu, Amal El-Naggar, Melanie Kogler, Luigi Tortola, Hai-Feng Zhang, Mariam Hassan, Michael M Lizardo, Sonia Hy Kung, Wan Lam, Josef M Penninger and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
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

11 authors at 2 institutions in 5 countries.

Busra TurguDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Amal El-NaggarDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Melanie KoglerInstitute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0001-8107-2441
Luigi TortolaInstitute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-8480-2080
Hai-Feng ZhangDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.ORCID 0000-0001-8215-1870
Mariam HassanDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Michael M LizardoDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Sonia Hy KungDepartment of Urological Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-9230-8939
Wan LamDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Josef M PenningerInstitute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-8194-3777
Poul H SorensenDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.ORCID 0000-0001-7447-2199
University of British Columbia · CAInstitute of Molecular Biotechnology · AT

Funding

Swiss National Science Foundation PBEZP3_145993
6 · The paper itself

Abstract

HACE1 is a HECT family E3 ubiquitin-protein ligase with broad but incompletely understood tumor suppressor activity. Here, we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase-dependent manner. Mechanistically, HACE1 binds to and ubiquitylates Ras-related C3 botulinum toxin substrate 1 (RAC1) when RAC1 is associated with mTOR complexes, including at focal adhesions, leading to proteasomal degradation of RAC1. This in turn decreases the stability of mTOR to reduce mTORC1 and mTORC2 activity. HACE1 deficient cells show enhanced mTORC1/2 activity, which is reversed by chemical or genetic RAC1 inactivation but not in cells expressing the HACE1-insensitive mutant, RAC1

Indexed as

Ubiquitin-Protein LigasesAnimalsMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceNeuropeptidesrac1 GTP-Binding ProteinTOR Serine-Threonine KinasesTumor Suppressor ProteinsUbiquitinHACE1 protein, mouseMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Neuropeptidesrac1 GTP-Binding ProteinRac1 protein, mouseTOR Serine-Threonine KinasesTumor Suppressor ProteinsUbiquitinUbiquitin-Protein LigasesE3 ubiquitin ligaseHACE1mTORC1 and mTORC2RAC1tumor suppressor gene

Identifiers

PMID37846480
PMCPMC10702814
OpenAlexW4387692503

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.