ArticleThe FEBS journal2014
HAUSP, a novel deubiquitinase for Rb - MDM2 the critical regulator.
Article in The FEBS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Overexpression and Biological Function of Ubiquitin-Specific Protease 42 in Gastric Cancer.PloS one · 2016Trial
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- S100A6 inhibits MDM2 to suppress breast cancer growth and enhance sensitivity to chemotherapy.Breast cancer research : BCR · 2023Article
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- USP7 targets XIAP for cancer progression: Establishment of a p53-independent therapeutic avenue for glioma.Oncogene · 2022Article
- Post-translational modifications on the retinoblastoma protein.Journal of biomedical science · 2022Review
- Targeting DNMTs to Overcome Enzalutamide Resistance in Prostate Cancer.Molecular cancer therapeutics · 2022Article
- RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells.Theranostics · 2022Article
- Review
- The Role of the Ubiquitin Proteasome System in Glioma: Analysis Emphasizing the Main Molecular Players and Therapeutic Strategies Identified in Glioblastoma Multiforme.Molecular neurobiology · 2021Review
- USP7 limits CDK1 activity throughout the cell cycle.The EMBO journal · 2021Article
- Metabolic Control by DNA Tumor Virus-Encoded Proteins.Pathogens (Basel, Switzerland) · 2021Review
- Integrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL).Scientific reports · 2021Article
- Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways.Frontiers in oncology · 2021Article
- Review
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
- USP7 Is a Master Regulator of Genome Stability.Frontiers in cell and developmental biology · 2020Review
- Ubiquitination of Nonhistone Proteins in Cancer Development and Treatment.Frontiers in oncology · 2020Review
- Nuclear deubiquitination in the spotlight: the multifaceted nature of USP7 biology in disease.Current opinion in cell biology · 2019Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor suppressor retinoblastoma-associated protein (Rb) is an important cell cycle regulator, arresting cells in early G1. It is commonly inactivated in cancers and its level is maintained during the cell cycle. Rb is regulated by various post-translational modifications such as phosphorylation, acetylation, ubiquitination and so on. Several E3 ligases including murine double minute 2 (MDM2) promote the degradation of Rb. This study focuses on the role of HAUSP (herpes virus associated ubiquitin specific protease) on Rb. Here, we show that HAUSP colocalizes and interacts with Rb to stabilize it from proteasomal degradation by removing wild-type and K48-linked ubiquitin chains in human embryonic kidney 293 (HEK293) cells. HAUSP deubiquitinates Rb in vivo and in vitro, leading to an increased cell population in the G1 phase. Hence, HAUSP is a novel deubiquitinase for Rb. Immunohistochemistry, western blotting and cell-based assays show that HAUSP is overexpressed in glioma and contributes towards glioma progression. However, HAUSP activity on Rb is abrogated in glioma (cancer), where these two proteins show an inverse relationship. MDM2 (a known substrate of HAUSP) serves as a better target for HAUSP-mediated deubiquitination in cancer cells, facilitating degradation of Rb and oncogenic progression. This novel regulatory axis is proteasome mediated, p53 independent, and the level of MDM2 is critical. The shift in equilibrium by differential deubiquitination in regulation of Rb explains a subtle difference existing between normal and cancer cells. This leads to speculation about a new possibility for distinguishing cancer cells from normal cells at the molecular level, which may be investigated for therapeutic intervention in the future.
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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.