Evidence map›Paper›PMID 27890708›Full record

ArticleNeurobiology of disease2017

Fbxl18 targets LRRK2 for proteasomal degradation and attenuates cell toxicity.

Xiaodong Ding, Sandeep K Barodia, Lisha Ma, Matthew S Goldberg

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

Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. FBXL18 increases cell proliferation and reduces cell radiosensitivity in esophageal squamous cell carcinoma.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2025
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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

4 authors at 2 institutions in 1 country.

Xiaodong DingDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sandeep K BarodiaCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Lisha MaDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Matthew S GoldbergDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: mattgoldberg@uab.edu.
The University of Texas Southwestern Medical Center · USUniversity of Alabama at Birmingham · US

Funding

Biophysical analysis of LRRK2R21NS072754 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI GOLDBERG, MATTHEW S, JAMESON, DAVID MICHAEL · 2011 to 2012
$435k
NINDS NIH HHS R21 NS072754
6 · The paper itself

Abstract

Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of familial Parkinson's disease (PD) and LRRK2 polymorphisms are associated with increased risk for idiopathic PD. However, the molecular mechanisms by which these mutations cause PD remain uncertain. In vitro studies indicate that disease-linked mutations in LRRK2 increase LRRK2 kinase activity and LRRK2-mediated cell toxicity. Identifying LRRK2-interacting proteins and determining their effects on LRRK2 are important for understanding LRRK2 function and for delineating the pathophysiological mechanisms of LRRK2 mutations. Here we identified a novel protein, F-box and leucine-rich repeat domain-containing protein 18 (Fbxl18) that physically associates with LRRK2. We demonstrated that Fbxl18 is a component of a Skp1-Cullin1-F-box ubiquitin ligase complex that regulates the abundance of LRRK2 by selectively targeting phosphorylated LRRK2 for ubiquitination and proteasomal degradation. Knockdown of endogenous Fbxl18 stabilized LRRK2 abundance while protein kinase C activation enhanced LRRK2 degradation by Fbxl18. Dephosphorylation of LRRK2 blocked Fbxl18 association with LRRK2. Taken together, we have identified potential mechanisms for LRRK2 regulation by kinase signaling pathways. Furthermore, Fbxl18 prevented caspase activation and cell death caused by LRRK2 and PD-linked mutant LRRK2. This reveals novel targets for developing potential therapies for familial and idiopathic PD.

Indexed as

AnimalsBrainCell DeathCell Line, TumorCell SurvivalChlorocebus aethiopsCOS CellsF-Box ProteinsHEK293 CellsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MiceNeuronsNIH 3T3 CellsProteasome Endopeptidase ComplexF-Box ProteinsFBXL18 protein, humanFbxl18 protein, mouseFBXO7 protein, humanLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanLrrk2 protein, mouseProteasome Endopeptidase ComplexCell deathKinaseLRRK2

Identifiers

PMID27890708
PMCPMC5718210
OpenAlexW2550255127

What OpenQuestion holds

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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.