ArticleScientific reports2015
iRhom1 regulates proteasome activity via PAC1/2 under ER stress.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Systematic analysis of the Frazzled receptor interactome establishes previously unreported regulators of axon guidance.Development (Cambridge, England) · 2023Article
- Yeast derlin Dfm1 employs a chaperone-like function to resolve misfolded membrane protein stress.PLoS biology · 2023Article
- Alternative splicing of the human rhomboid family-1 gene RHBDF1 inhibits epidermal growth factor receptor activation.The Journal of biological chemistry · 2022Article
- iRhom pseudoproteases regulate ER stress-induced cell death through IPNature communications · 2022Article
- Novel compound C150 inhibits pancreatic cancer through induction of ER stress and proteosome assembly.Frontiers in oncology · 2022Article
- Inflammatory activation of surface molecule shedding by upregulation of the pseudoprotease iRhom2 in colon epithelial cells.Scientific reports · 2021Article
- RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression.Cancer cell international · 2021Article
- Expanding the role of proteasome homeostasis in Parkinson's disease: beyond protein breakdown.Cell death & disease · 2021Review
- Proteasome Complexes and Their Heterogeneity in Colorectal, Breast and Pancreatic Cancers.Journal of Cancer · 2021Article
- The Function ofBiology · 2020Article
- The role of rhomboid superfamily members in protein homeostasis: Mechanistic insight and physiological implications.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Review
- Article
- Regulation of proteasome assembly and activity in health and disease.Nature reviews. Molecular cell biology · 2018Review
- TOM1 Regulates Neuronal Accumulation of Amyloid-β Oligomers by FcγRIIb2 Variant in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Human rhomboid family-1 modulates clathrin coated vesicle-dependent pro-transforming growth factor α membrane trafficking to promote breast cancer progression.EBioMedicine · 2018Article
- PERM Hypothesis: The Fundamental Machinery Able to Elucidate the Role of Xenobiotics and Hormesis in Cell Survival and Homeostasis.International journal of molecular sciences · 2017Review
- Tuning the proteasome to brighten the end of the journey.American journal of physiology. Cell physiology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasome is a protein degradation complex that plays a major role in maintaining cellular homeostasis. Despite extensive efforts to identify protein substrates that are degraded through ubiquitination, the regulation of proteasome activity itself under diverse signals is poorly understood. In this study, we have isolated iRhom1 as a stimulator of proteasome activity from genome-wide functional screening using cDNA expression and an unstable GFP-degron. Downregulation of iRhom1 reduced enzymatic activity of proteasome complexes and overexpression of iRhom1 enhanced it. Native-gel and fractionation analyses revealed that knockdown of iRhom1 expression impaired the assembly of the proteasome complexes. The expression of iRhom1 was increased by endoplasmic reticulum (ER) stressors, such as thapsigargin and tunicamycin, leading to the enhancement of proteasome activity, especially in ER-containing microsomes. iRhom1 interacted with the 20S proteasome assembly chaperones PAC1 and PAC2, affecting their protein stability. Moreover, knockdown of iRhom1 expression impaired the dimerization of PAC1 and PAC2 under ER stress. In addition, iRhom1 deficiency in D. melanogaster accelerated the rough-eye phenotype of mutant Huntingtin, while transgenic flies expressing either human iRhom1 or Drosophila iRhom showed rescue of the rough-eye phenotype. Together, these results identify a novel regulator of proteasome activity, iRhom1, which functions via PAC1/2 under ER stress.
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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.