ArticleAutophagy2021
Crosstalk between HSPA5 arginylation and sequential ubiquitination leads to AKT degradation through autophagy flux.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis.Frontiers in cell and developmental biology · 2020Pooled it
- FTSJ3-Mediated 2'-O-Methylation of HSPA5 mRNA Stabilizes BOP1 via SUMOylation to Drive DRP1-Dependent Mitochondrial Fission and Fatty Acid Oxidation in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- MAPL regulates gasdermin-mediated release of mtDNA from lysosomes to drive pyroptotic cell death.Nature cell biology · 2025Article
- ATE1 promotes breast cancer progression via arginylation-dependent regulation of MAPK-MYC signaling.Cell communication and signaling : CCS · 2025Article
- TBK1 is a signaling hub in coordinating stress-adaptive mechanisms in head and neck cancer progression.Autophagy · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in tumor cells in an USP7/AKT/GSK-3β pathway-dependent manner.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS-induced colitis in a murine model.Journal of extracellular vesicles · 2024Article
- B-Myb deficiency boosts bortezomib-induced immunogenic cell death in colorectal cancer.Scientific reports · 2024Article
- The Ubiquitin-Proteasome System in Tumor Metabolism.Cancers · 2023Review
- NLRC5 restricts dengue virus infection by promoting the autophagic degradation of viral NS3 through E3 ligase CUL2 (cullin 2).Autophagy · 2023Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Article
- Myristate induces mitochondrial fragmentation and cardiomyocyte hypertrophy through mitochondrial E3 ubiquitin ligase MUL1.Frontiers in cell and developmental biology · 2023Article
- Article
- Proteolysis Targeting Chimeras (PROTACs): A Perspective on Integral Membrane Protein Degradation.ACS pharmacology & translational science · 2022Review
- Autophagy induction promoted by mNature communications · 2022Article
- Current methodologies in protein ubiquitination characterization: from ubiquitinated protein to ubiquitin chain architecture.Cell & bioscience · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AKT/PKB is downregulated by the ubiquitin-proteasome system (UPS), which plays a key role in cell survival and tumor progression in various types of cancer. The objective of this study was to determine the relationship between the sequential ubiquitination of lysine residues K284 to K214 in AKT and R-HSPA5 (the arginylated form of HSPA5), which contribute to the autophagic/lysosomal degradation of AKT when impaired proteasomal activity induces cellular stress. Results show that proteasome inhibitors (PIs) increased ATE1 (arginyltransferase 1)-mediated R-HSPA5 levels in a reactive oxygen species (ROS)-dependent manner. Further, binding of fully ubiquitinated AKT with R-HSPA5 induced AKT degradation via the autophagy-lysosome pathway. Specifically, the K48 (Lys48)-linked ubiquitinated form of AKT was selectively degraded in the lysosome with R-HSPA5. The deubiquitinase, USP7 (ubiquitin specific peptidase 7), prevented AKT degradation by inhibiting AKT ubiquitination via interaction with AKT. MUL1 (mitochondrial ubiquitin ligase activator of NFKB 1) also played a vital role in the lysosomal degradation of AKT by sequentially ubiquitinating AKT residues K284 to K214 for R-HSPA5-mediated autophagy. Consistent with this finding, despite HSPA5 arginylation, AKT was not degraded in
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