ArticleMolecular biology of the cell2006
The slow Wallerian degeneration protein, WldS, binds directly to VCP/p97 and partially redistributes it within the nucleus.
Article in Molecular biology of the cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 61 citations in OpenAlex.
- Diabetic Polyneuropathy: New Strategies to Target Sensory Neurons in Dorsal Root Ganglia.International journal of molecular sciences · 2023Review
- Neuroprotection in Glaucoma: NADCells · 2021Review
- Experimental Model Systems for Understanding Human Axonal Injury Responses.International journal of molecular sciences · 2021Review
- Emergence of SARM1 as a Potential Therapeutic Target for Wallerian-type Diseases.Cell chemical biology · 2020Review
- p97 Composition Changes Caused by Allosteric Inhibition Are Suppressed by an On-Target Mechanism that Increases the Enzyme's ATPase Activity.Cell chemical biology · 2016Article
- Local axonal protection by WldS as revealed by conditional regulation of protein stability.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Signaling mechanisms regulating Wallerian degeneration.Current opinion in neurobiology · 2014Review
- NEDD8 ultimate buster-1 long (NUB1L) protein promotes transfer of NEDD8 to proteasome for degradation through the P97UFD1/NPL4 complex.The Journal of biological chemistry · 2013Article
- Intrinsic axonal degeneration pathways are critical for glaucomatous damage.Experimental neurology · 2013Review
- Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain.PloS one · 2013Article
- UBE4B: a promising regulatory molecule in neuronal death and survival.International journal of molecular sciences · 2012Review
- Axon degeneration: molecular mechanisms of a self-destruction pathway.The Journal of cell biology · 2012Review
- Wld(S), Nmnats and axon degeneration--progress in the past two decades.Protein & cell · 2010Review
- Wallerian degeneration, wld(s), and nmnat.Annual review of neuroscience · 2010Review
- Transgenic mice expressing the Nmnat1 protein manifest robust delay in axonal degeneration in vivo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Nicotinamide mononucleotide adenylyltransferase expression in mitochondrial matrix delays Wallerian degeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Valosin-containing protein disease: inclusion body myopathy with Paget's disease of the bone and fronto-temporal dementia.Neuromuscular disorders : NMD · 2009Review
- Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice.The Journal of cell biology · 2009Article
- Wld S requires Nmnat1 enzymatic activity and N16-VCP interactions to suppress Wallerian degeneration.The Journal of cell biology · 2009Article
- Non-nuclear Wld(S) determines its neuroprotective efficacy for axons and synapses in vivo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Slow Wallerian degeneration (Wld(S)) mutant mice express a chimeric nuclear protein that protects sick or injured axons from degeneration. The C-terminal region, derived from NAD(+) synthesizing enzyme Nmnat1, is reported to confer neuroprotection in vitro. However, an additional role for the N-terminal 70 amino acids (N70), derived from multiubiquitination factor Ube4b, has not been excluded. In wild-type Ube4b, N70 is part of a sequence essential for ubiquitination activity but its role is not understood. We report direct binding of N70 to valosin-containing protein (VCP; p97/Cdc48), a protein with diverse cellular roles including a pivotal role in the ubiquitin proteasome system. Interaction with Wld(S) targets VCP to discrete intranuclear foci where ubiquitin epitopes can also accumulate. Wld(S) lacking its N-terminal 16 amino acids (N16) neither binds nor redistributes VCP, but continues to accumulate in intranuclear foci, targeting its intrinsic NAD(+) synthesis activity to these same foci. Wild-type Ube4b also requires N16 to bind VCP, despite a more C-terminal binding site in invertebrate orthologues. We conclude that N-terminal sequences of Wld(S) protein influence the intranuclear location of both ubiquitin proteasome and NAD(+) synthesis machinery and that an evolutionary recent sequence mediates binding of mammalian Ube4b to VCP.
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.