Evidence map›Paper›PMID 29694895›Full record

ArticleCell reports2018

Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization.

Hiroaki Fujita, Akira Tokunaga, Satoshi Shimizu, Amanda L Whiting, Francisco Aguilar-Alonso, Kenji Takagi, Erik Walinda, Yoshiteru Sasaki, Taketo Shimokawa, Tsunehiro Mizushima and 6 more

Abstract read
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
–field-weighted citation impact
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

65 citing papers in PubMed.

  1. Article
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  9. Review
  10. Article
  11. Article
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  14. HOIL1 mediates MDA5 activation through ubiquitination of LGP2.bioRxiv : the preprint server for biology · 2024
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

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

16 authors.

Hiroaki FujitaDepartment of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto 606-8501, Japan.
Akira TokunagaDepartment of Molecular Engineering, Kyoto University School of Engineering, Kyoto 615-8510, Japan.
Satoshi ShimizuDepartment of Anesthesia, Kyoto University Hospital, Kyoto 606-8507, Japan.
Amanda L WhitingLaboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Francisco Aguilar-AlonsoLaboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Kenji TakagiDepartment of Picobiology, University of Hyogo School of Life Science, Hyogo 678-1297, Japan.
Erik WalindaDepartment of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto 606-8501, Japan.
Yoshiteru SasakiDepartment of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto 606-8501, Japan.
Taketo ShimokawaDepartment of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto 606-8501, Japan.
Tsunehiro MizushimaDepartment of Picobiology, University of Hyogo School of Life Science, Hyogo 678-1297, Japan.
Izuru OhkiDepartment of Molecular Engineering, Kyoto University School of Engineering, Kyoto 615-8510, Japan.
Mariko AriyoshiDepartment of Molecular Engineering, Kyoto University School of Engineering, Kyoto 615-8510, Japan.
Hidehito TochioDepartment of Biophysics, Kyoto University School of Science, Kyoto 606-8502, Japan.
Federico BernalLaboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Masahiro ShirakawaDepartment of Molecular Engineering, Kyoto University School of Engineering, Kyoto 615-8510, Japan.
Kazuhiro IwaiDepartment of Molecular and Cellular Physiology, Kyoto University School of Medicine, Kyoto 606-8501, Japan. Electronic address: kiwai@mcp.med.kyoto-u.ac.jp.

Funding

Chemical Targeting of Multi-Protein ComplexesZIABC011511 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BERNAL, FEDERICO · 2013 to 2019
$1.4M
Intramural NIH HHS ZIA BC011511
6 · The paper itself

Abstract

The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics.

Indexed as

Amino Acid MotifsAnimalsCarrier ProteinsCrystallography, X-RayIntracellular Signaling Peptides and ProteinsMiceMultiprotein ComplexesPolyubiquitinProtein DomainsProtein Structure, QuaternaryUbiquitin-Protein LigasesCarrier ProteinsIntracellular Signaling Peptides and ProteinsMultiprotein ComplexesPolyubiquitinRbck1 protein, mouseSipl1 protein, mouseUbiquitin-Protein LigasescancerHOIL-1LHOIPlinear ubiquitin chainsLUBACLUBAC-tethering motifSHARPINubiquitin-associated domainubiquitin-like domain

Identifiers

PMID29694895
PMCPMC6044281

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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.