ArticleThe Journal of biological chemistry2016
The Proteasome Ubiquitin Receptor hRpn13 and Its Interacting Deubiquitinating Enzyme Uch37 Are Required for Proper Cell Cycle Progression.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target.Nature communications · 2025Article
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- A structure-based designed small molecule depletes hRpn13Nature communications · 2024Article
- hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-κB p50.Molecular cell · 2024Article
- Development and anticancer properties of Up284, a spirocyclic candidate ADRM1/RPN13 inhibitor.PloS one · 2023Article
- Proteasome substrate receptors and their therapeutic potential.Trends in biochemical sciences · 2022Review
- Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma.Nature communications · 2021Article
- Article
- ADRM1 as a therapeutic target in hepatocellular carcinoma.The Kaohsiung journal of medical sciences · 2021Article
- Proteasome-Bound UCH37/UCHL5 Debranches Ubiquitin Chains to Promote Degradation.Molecular cell · 2020Article
- Mechanistic Studies of the Multiple Myeloma and Melanoma Cell-Selective Toxicity of the Rpn13-Binding Peptoid KDT-11.Cell chemical biology · 2020Article
- Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190.Cell chemical biology · 2020Article
- Impact of Losing hRpn13 Pru or UCHL5 on Proteasome Clearance of Ubiquitinated Proteins and RA190 Cytotoxicity.Molecular and cellular biology · 2020Article
- Unveiling the immunomodulatory properties of Haemonchus contortus adhesion regulating molecule 1 interacting with goat T cells.Parasites & vectors · 2020Article
- Deubiquitination Reactions on the Proteasome for Proteasome Versatility.International journal of molecular sciences · 2020Review
- An Extended Conformation for K48 Ubiquitin Chains Revealed by the hRpn2:Rpn13:K48-Diubiquitin Structure.Structure (London, England : 1993) · 2020Article
- Drug Development Targeting the Ubiquitin-Proteasome System (UPS) for the Treatment of Human Cancers.Cancers · 2020Review
- Structure of E3 ligase E6AP with a proteasome-binding site provided by substrate receptor hRpn10.Nature communications · 2020Article
- Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease.Molecules (Basel, Switzerland) · 2020Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Recently, we reported that bisbenzylidine piperidone RA190 adducts to Cys-88 of the proteasome ubiquitin receptor hRpn13, triggering accumulation of ubiquitinated proteins and endoplasmic reticulum stress-related apoptosis in various cancer cell lines. hRpn13 contains an N-terminal pleckstrin-like receptor for ubiquitin domain that binds ubiquitin and docks it into the proteasome as well as a C-terminal deubiquitinase adaptor (DEUBAD) domain that binds the deubiquitinating enzyme Uch37. Here we report that hRpn13 and Uch37 are required for proper cell cycle progression and that their protein knockdown leads to stalling at G0/G1 Moreover, serum-starved cells display reduced hRpn13 and Uch37 protein levels with hallmarks of G0/G1 stalling and recovery to their steady-state protein levels following release from nutrient deprivation. Interestingly, loss of hRpn13 correlates with a small but statistically significant reduction in Uch37 protein levels, suggesting that hRpn13 interaction may stabilize this deubiquitinating enzyme in human cells. We also find that RA190 treatment leads to a loss of S phase, suggesting a block of DNA replication, and G2 arrest by using fluorescence-activated cell sorting. Uch37 deprivation further indicated a reduction of DNA replication and G0/G1 stalling. Overall, this work implicates hRpn13 and Uch37 in cell cycle progression, providing a rationale for their function in cellular proliferation and for the apoptotic effect of the hRpn13-targeting molecule RA190.
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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.