ArticleMolecular cell2021
Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Mechanism of K63-linked polyubiquitin recognition and cleavage by the BRCA1-A complex.Nature communications · 2026Article
- ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition.Nature communications · 2026Article
- The EF-hand domain of MINDY3 is a ubiquitin and RAD23 UBL-binding domain.EMBO reports · 2026Article
- Shared genetic architecture between Alzheimer's disease and psychiatric disorders revealed by multi-trait genome-wide analyses.BMC medical genomics · 2026Article
- Fine-Tuning Protein Fate: Mechanisms of E1, E2, and E3 Enzymes and Deubiquitinases in Cell Signaling.International journal of molecular sciences · 2026Review
- Complexes Formed by the K63-Specific Deubiquitinating Enzyme BRCC36: New Promising Therapeutic Targets in Human Disease.Biomolecules · 2025Review
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- Structural and functional insights into Ubl domain-mediated regulation of SARS-CoV-2 PLpro.Biology direct · 2025Article
- Structural visualization of HECT-type E3 ligase Ufd4 accepting and transferring ubiquitin to form K29/K48-branched polyubiquitination.Nature communications · 2025Article
- Discovery and mechanism of K63-linkage-directed deubiquitinase activity in USP53.Nature chemical biology · 2025Article
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- MINDY1 Induces PD-L1 Deubiquitination to Promote Immune Escape in Hepatocellular Carcinoma by the Wnt/β-Catenin Pathway.Oncology research · 2025Article
- Study on the mechanism of liver cancer immune escape mediated by MINDY1 through regulation of PD-L1 ubiquitination level.Biomolecules & biomedicine · 2024Article
- VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.Nature structural & molecular biology · 2024Article
- Linkage-specific ubiquitin binding interfaces modulate the activity of the chlamydial deubiquitinase Cdu1 towards poly-ubiquitin substrates.PLoS pathogens · 2024Article
- K48- and K63-linked ubiquitin chain interactome reveals branch- and length-specific ubiquitin interactors.Life science alliance · 2024Article
- Ubiquitin recruiting chimera: more than just a PROTAC.Biology direct · 2024Review
- Applications of protein ubiquitylation and deubiquitylation in drug discovery.The Journal of biological chemistry · 2024Review
- Structural insights into ubiquitin chain cleavage byLife science alliance · 2023Article
- The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway.Frontiers in oncology · 2023Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Of the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins being targeted for degradation. MINDY1 and MINDY2 are members of the MINDY family of deubiquitinases (DUBs) that have exquisite specificity for cleaving K48-polyUb, yet we have a poor understanding of their catalytic mechanism. Here, we analyze the crystal structures of MINDY1 and MINDY2 alone and in complex with monoUb, di-, and penta-K48-polyUb, identifying 5 distinct Ub binding sites in the catalytic domain that explain how these DUBs sense both Ub chain length and linkage type to cleave K48-polyUb chains. The activity of MINDY1/2 is inhibited by the Cys-loop, and we find that substrate interaction relieves autoinhibition to activate these DUBs. We also find that MINDY1/2 use a non-canonical catalytic triad composed of Cys-His-Thr. Our findings highlight multiple layers of regulation modulating DUB activity in MINDY1 and MINDY2.
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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.