Evidence map›Paper›PMID 30795516›Full record

ArticleInternational journal of molecular sciences2019

Regulation of c-Raf Stability through the CTLH Complex.

Christina J McTavish, Wesley Bérubé-Janzen, Xu Wang, Matthew E R Maitland, Louisa M Salemi, David A Hess, Caroline Schild-Poulter

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

15 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation.Journal of experimental & clinical cancer research : CR · 2025
    Article
  3. Article
  4. Article
  5. Muskelin acts as a substrate receptor of the highly regulatedbioRxiv : the preprint server for biology · 2024
    Article
  6. Article
  7. Novel loss-of-function variants inFrontiers in pediatrics · 2024
    Article
  8. Review
  9. Article
  10. Structural and Functional Insights into GID/CTLH E3 Ligase Complexes.International journal of molecular sciences · 2022
    Review
  11. Proteomic analysis of ubiquitination substrates reveals a CTLH E3 ligase complex-dependent regulation of glycolysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  12. Article
  13. Recognition of nonproline N-terminal residues by the Pro/N-degron pathway.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Article
  15. Review
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

7 authors at 1 institution in 1 country.

Christina J McTavishRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5B7, Canada. christina.mctavish@gmail.com.
Wesley Bérubé-JanzenRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5B7, Canada. wesleyjanzen@hotmail.com.
Xu WangRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5B7, Canada. xwang287@uwo.ca.
Matthew E R MaitlandRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5B7, Canada. mmaitla2@uwo.ca.
Louisa M SalemiRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5B7, Canada. louisa.salemi@gmail.com.
David A HessRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5B7, Canada. dhess@robarts.ca.
Caroline Schild-PoulterRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5B7, Canada. cschild-poulter@robarts.ca.ORCID 0000-0001-9943-9942
Western University · CA

Funding

Canadian Institutes of Health Research MOP-114958 and MOP-142414Natural Sciences and Engineering Research Council of Canada PGSD2 - 519042 - 2018
6 · The paper itself

Abstract

c-Raf is a central component of the extracellular signal-regulated kinase (ERK) pathway which is implicated in the development of many cancer types. RanBPM (Ran-Binding Protein M) was previously shown to inhibit c-Raf expression, but how this is achieved remains unclear. RanBPM is part of a recently identified E3 ubiquitin ligase complex, the CTLH (C-terminal to LisH) complex. Here, we show that the CTLH complex regulates c-Raf expression through a control of its degradation. Several domains of RanBPM were found necessary to regulate c-Raf levels, but only the C-terminal CRA (CT11-RanBPM) domain showed direct interaction with c-Raf. c-Raf ubiquitination and degradation is promoted by the CTLH complex. Furthermore, A-Raf and B-Raf protein levels are also regulated by the CTLH complex, indicating a common regulation of Raf family members. Finally, depletion of CTLH subunits RMND5A (required for meiotic nuclear division 5A) and RanBPM resulted in enhanced proliferation and loss of RanBPM promoted tumour growth in a mouse model. This study uncovers a new mode of control of c-Raf expression through regulation of its degradation by the CTLH complex. These findings also uncover a novel target of the CTLH complex, and suggest that the CTLH complex has activities that suppress cell transformation and tumour formation.

Indexed as

ProteolysisAdaptor Proteins, Signal TransducingAnimalsCells, CulturedCytoskeletal ProteinsEnzyme StabilityHEK293 CellsHeLa CellsHumansMiceMice, Inbred NODMice, SCIDNuclear ProteinsProto-Oncogene Proteins c-rafUbiquitinationAdaptor Proteins, Signal TransducingCytoskeletal ProteinsNuclear ProteinsProto-Oncogene Proteins c-rafRan binding protein 9cancerc-RafCTLH complexERK pathwayRanBPMRMND5Aubiquitination

Identifiers

PMID30795516
PMCPMC6412545
OpenAlexW2917086903

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.