ArticleJournal of cell science2014
Ubiquitylation and activation of a Rab GTPase is promoted by a β₂AR-HACE1 complex.
Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Faecalibacterium prausnitzii enzyme reprograms PD-L1 trafficking and sensitizes colorectal cancer to immunotherapy in mice.Nature microbiology · 2026Article
- A proximity map of RAB GTPases delineates roles for RAB14 in EARP complex and UHRF1BP1 endosomal recruitments.Communications biology · 2025Article
- Article
- Cross-family small GTPase ubiquitination by the intracellular pathogenMolecular biology of the cell · 2024Article
- Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1.Nature structural & molecular biology · 2024Article
- p97/VCP Promotes the Recycling of Endocytic Cargo.Molecular biology of the cell · 2023Article
- Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Ubiquitin and its relatives as wizards of the endolysosomal system.Journal of cell science · 2023Article
- Membrane Targeting and GTPase Activity of Rab7 Are Required for Its Ubiquitination by RNF167.International journal of molecular sciences · 2022Article
- Review
- Ubiquitination-Dependent Regulation of Small GTPases in Membrane Trafficking: From Cell Biology to Human Diseases.Frontiers in cell and developmental biology · 2021Review
- Rab family of small GTPases: an updated view on their regulation and functions.The FEBS journal · 2021Review
- Rabs in Signaling and Embryonic Development.International journal of molecular sciences · 2020Review
- L-type prostaglandin D synthase regulates the trafficking of the PGDThe Journal of biological chemistry · 2019Article
- HACE1, RAC1, and what else in the pathogenesis of SPPRS?Neurology. Genetics · 2019Article
- Demethylation of the HACE1 gene promoter inhibits the proliferation of human liver cancer cells.Oncology letters · 2019Article
- Post translational modifications of Rab GTPases.Small GTPases · 2018Review
- Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
We and others have shown that trafficking of G-protein-coupled receptors is regulated by Rab GTPases. Cargo-mediated regulation of vesicular transport has received great attention lately. Rab GTPases, which form the largest branch of the Ras GTPase superfamily, regulate almost every step of vesicle-mediated trafficking. Rab GTPases are well-recognized targets of human diseases but their regulation and the mechanisms connecting them to cargo proteins are still poorly understood. Here, we show by overexpression and depletion studies that HACE1, a HECT-domain-containing ubiquitin ligase, promotes the recycling of the β₂-adrenergic receptor (β₂AR), a prototypical G-protein-coupled receptor, through a Rab11a-dependent mechanism. Interestingly, the β₂AR in conjunction with HACE1 triggered ubiquitylation of Rab11a, as observed by western blot analysis. LC-MS/MS experiments determined that Rab11a is ubiquitylated on Lys145. A Rab11a-K145R mutant failed to undergo β₂AR-HACE1-induced ubiquitylation and inhibited the HACE1-mediated recycling of the β₂AR. Rab11a, but not Rab11a-K145R, was activated by β₂AR-HACE1, indicating that ubiquitylation of Lys145 is involved in activation of Rab11a. Co-expression of β₂AR-HACE1 also potentiated ubiquitylation of Rab6a and Rab8a, but not of other Rab GTPases that were tested. We report a novel regulatory mechanism of Rab GTPases through their ubiquitylation, with associated functional effects demonstrated on Rab11a. This suggests a new pathway whereby a cargo protein, such as a G-protein-coupled receptor, can regulate its own trafficking by inducing the ubiquitylation and activation of a Rab GTPase.
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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.