ArticlePLoS pathogens2018
SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- YAP Inhibits HIV-1 transcription and promotes HIV-1 latency by regulating E3 ubiquitin ligase UHRF1 mediated tat degradation.PLoS pathogens · 2026Article
- Therapeutic Potential of the Deubiquitinase BRCC3 in Attenuating Ischemic Myocardial Injury and Ventricular Remodeling.Research (Washington, D.C.) · 2026Article
- USP45-mediated deubiquitination of HIV-1 Tat regulates viral transcription and latency.Frontiers in microbiology · 2026Article
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Complexes Formed by the K63-Specific Deubiquitinating Enzyme BRCC36: New Promising Therapeutic Targets in Human Disease.Biomolecules · 2025Review
- Plasma Proteome Profiling Reveals Inflammation Markers and Tafamidis Effects in V30M Transthyretin Polyneuropathy.International journal of molecular sciences · 2025Article
- TargetSeeker-MS: A Bayesian Inference Approach for Drug-Target Discovery Using Protein Fractionation Coupled to Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2025Article
- Upregulated Expression of SHMT2 Predicts Poor Survival of Lung Adenocarcinoma.Genetics research · 2025Article
- Review
- A tick saliva serpin, IxsS17 inhibits host innate immune system proteases and enhances host colonization by Lyme disease agent.PLoS pathogens · 2024Article
- Deubiquitinase USP1 regulates sarbecovirus ORF6 protein function.Journal of virology · 2024Article
- BRISC is required for optimal activation of NF-κB in Kupffer cells induced by LPS and contributes to acute liver injury.Cell death & disease · 2023Article
- SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1.International journal of biological sciences · 2023Article
- A siRNA screening of UBE2 family demonstrated that UBE2R1 had a high repressive effect on HIV Tat protein.Biochemistry and biophysics reports · 2022Article
- Host Cell Redox Alterations Promote Latent HIV-1 Reactivation through Atypical Transcription Factor Cooperativity.Viruses · 2022Article
- Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.Biomolecules · 2022Review
- Deubiquitinases in cell death and inflammation.The Biochemical journal · 2022Review
- Article
- An update of label-free protein target identification methods for natural active products.Theranostics · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
HIV-1 Tat is a key regulator of viral transcription, however little is known about the mechanisms that control its turnover in T cells. Here we use a novel proteomics technique, called DiffPOP, to identify the molecular target of JIB-04, a small molecule compound that potently and selectively blocks HIV-1 Tat expression, transactivation, and virus replication in T cell lines. Mass-spectrometry analysis of whole-cell extracts from 2D10 Jurkat T cells revealed that JIB-04 targets Serine Hydroxymethyltransferase 2 (SHMT2), a regulator of glycine biosynthesis and an adaptor for the BRCC36 K63Ub-specific deubiquitinase in the BRISC complex. Importantly, knockdown of SHMT1,2 or BRCC36, or exposure of cells to JIB-04, strongly increased Tat K63Ub-dependent destruction via autophagy. Moreover, point mutation of multiple lysines in Tat, or knockdown of BRCC36 or SHMT1,2, was sufficient to prevent destruction of Tat by JIB-04. We conclude that HIV-1 Tat levels are regulated through K63Ub-selective autophagy mediated through SHMT1,2 and the BRCC36 deubiquitinase.
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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.