ArticlePLoS genetics2014
RPM-1 uses both ubiquitin ligase and phosphatase-based mechanisms to regulate DLK-1 during neuronal development.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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.
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.
Who cites it
36 citing papers in PubMed, 46 citations in OpenAlex.
- Elevated mitochondrial superoxide promotes longevity through a mitochondria-to-nucleus kinase signaling pathway.Redox biology · 2026Article
- Comparative analysis of neuronal proteolytic pathways reveals neuron-specific and sub-compartmental-specific capacities with aging.Cellular and molecular life sciences : CMLS · 2026Article
- MAK-2 Kinase Is Required for Extended Longevity and Enhanced Stress Resistance Resulting From Mild Impairment of Mitochondrial Function in isp-1 Mutants.Aging cell · 2026Article
- Integrin adhesome axis inhibits the RPM-1 ubiquitin ligase signaling hub to regulate growth cone and axon development.PLoS genetics · 2024Article
- Molecular regulation of axon termination in mechanosensory neurons.Development (Cambridge, England) · 2024Review
- Review
- Article
- Axon development is regulated at genetic and proteomic interfaces between the integrin adhesome and the RPM-1 ubiquitin ligase signaling hub.bioRxiv : the preprint server for biology · 2023Article
- Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function.bioRxiv : the preprint server for biology · 2023Article
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
- Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects.Brain : a journal of neurology · 2023Article
- Article
- A cilia-independent function of BBSome mediated by DLK-MAPK signaling in C. elegans photosensation.Developmental cell · 2022Article
- Ubiquitin ligase activity inhibits Cdk5 to control axon termination.PLoS genetics · 2022Article
- O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 modulate seizure susceptibility in C. elegans.PloS one · 2021Article
- Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease.Neural development · 2020Review
- Autophagy is inhibited by ubiquitin ligase activity in the nervous system.Nature communications · 2019Article
- Apoptotic cell death regulation in neurons.The FEBS journal · 2019Review
- An axonal stress response pathway: degenerative and regenerative signaling by DLK.Current opinion in neurobiology · 2018Review
- RPM-1 and DLK-1 regulate pioneer axon outgrowth by controlling Wnt signaling.Development (Cambridge, England) · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The Pam/Highwire/RPM-1 (PHR) proteins are key regulators of neuronal development that function in axon extension and guidance, termination of axon outgrowth, and synapse formation. Outside of development, the PHR proteins also regulate axon regeneration and Wallerian degeneration. The PHR proteins function in part by acting as ubiquitin ligases that degrade the Dual Leucine zipper-bearing Kinase (DLK). Here, we show that the Caenorhabditis elegans PHR protein, Regulator of Presynaptic Morphology 1 (RPM-1), also utilizes a phosphatase-based mechanism to regulate DLK-1. Using mass spectrometry, we identified Protein Phosphatase Magnesium/Manganese dependent 2 (PPM-2) as a novel RPM-1 binding protein. Genetic, transgenic, and biochemical studies indicated that PPM-2 functions coordinately with the ubiquitin ligase activity of RPM-1 and the F-box protein FSN-1 to negatively regulate DLK-1. PPM-2 acts on S874 of DLK-1, a residue implicated in regulation of DLK-1 binding to a short, inhibitory isoform of DLK-1 (DLK-1S). Our study demonstrates that PHR proteins function through both phosphatase and ubiquitin ligase mechanisms to inhibit DLK. Thus, PHR proteins are potentially more accurate and sensitive regulators of DLK than originally thought. Our results also highlight an important and expanding role for the PP2C phosphatase family in neuronal development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.