ArticleMolecular and cellular biology2008
Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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98 citing papers in PubMed, 175 citations in OpenAlex.
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- Label-free proteomic analysis of Duchenne and Becker muscular dystrophy showed decreased sarcomere proteins and increased ubiquitination-related proteins.Scientific reports · 2025Article
- New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson's disease.Metabolic brain disease · 2025Review
- Rho/ROCK Pathway as a Therapeutic Target in Multiple Diseases.International journal of drug discovery and pharmacology · 2025Article
- Cytoskeleton dysfunction of motor neuron in spinal muscular atrophy.Journal of neurology · 2024Review
- Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.Frontiers in neuroscience · 2024Review
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- Profilin-1 regulates DNA replication forks in a context-dependent fashion by interacting with SNF2H and BOD1L.Nature communications · 2022Article
- RhoA Signaling in Neurodegenerative Diseases.Cells · 2022Review
- A Progressive Loss of phosphoSer138-Profilin Aligns with Symptomatic Course in the R6/2 Mouse Model of Huntington's Disease: Possible Sex-Dependent Signaling.Cellular and molecular neurobiology · 2022Article
- Mutant Huntingtin Protein Interaction Map Implicates Dysregulation of Multiple Cellular Pathways in Neurodegeneration of Huntington's Disease.Journal of Huntington's disease · 2022Article
- Profilin 1 Induces Tumor Metastasis by Promoting Microvesicle Secretion Through the ROCK 1/p-MLC Pathway in Non-Small Cell Lung Cancer.Frontiers in pharmacology · 2022Article
- Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA.Neuroscience insights · 2022Review
- Specificity and Redundancy of Profilin 1 and 2 Function in Brain Development and Neuronal Structure.Cells · 2021Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Y-27632, an inhibitor of the Rho-associated kinase ROCK, is a therapeutic lead for Huntington disease (HD). The downstream targets that mediate its inhibitory effects on huntingtin (Htt) aggregation and toxicity are unknown. We have identified profilin, a small actin-binding factor that also interacts with Htt, as being a direct target of the ROCK1 isoform. The overexpression of profilin reduces the aggregation of polyglutamine-expanded Htt and androgen receptor (AR) peptides. This requires profilin's G-actin binding activity and its direct interaction with Htt, which are both inhibited by the ROCK1-mediated phosphorylation of profilin at Ser-137. Y-27632 blocks the phosphorylation of profilin in HEK293 cells and primary neurons, which maintains profilin in an active state. The knockdown of profilin blocks the inhibitory effect of Y-27632 on both AR and Htt aggregation. A signaling pathway from ROCK1 to profilin thus controls polyglutamine protein aggregation and is targeted by a promising therapeutic lead for HD.
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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.