ArticleAutophagy2021
Hypoxia-induced acetylation of PAK1 enhances autophagy and promotes brain tumorigenesis via phosphorylating ATG5.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 176 citations in OpenAlex.
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- Identifying causal genetic variants for high-altitude adaptation through blood eQTL analysis in plateau populations.Communications biology · 2026Article
- Ubiquitin-specific protease 48 drives malignant progression of colorectal cancer by suppressing autophagy through stabilizing sequestosome 1.Cell death and differentiation · 2026Article
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- UBA1 promotes cardiac hypertrophy by suppressing autophagy via targeting ATG5 for ubiquitination.Cell communication and signaling : CCS · 2026Article
- OGT Silencing Protects against Trophoblast Ferroptosis in Gestational Diabetes Mellitus Via ELP3 O-GlcNAcylation Suppression.Applied biochemistry and biotechnology · 2026Article
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- miR-19b-3p regulates autophagy of BMSCs in hypoxia through PTEN/Akt/mTOR pathway to promote fracture healing.Journal of molecular histology · 2026Article
- A bibliometric analysis of global research trends in autophagy and glioblastomas.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- TRIM47-mediated Ubiquitination of p53 Controls Proliferative Progression and Stress Adaptation in Glioblastoma.International journal of biological sciences · 2026Article
- Acute Hypoxia Induces Cardiomyocyte Autophagy via SIRT5/mTOR/ULK1 Pathway.BioMed research international · 2026Article
- Hypoxic Reprogramming of ACOX1-Driven HSP90AB1 Crotonylation Stabilizes Thioredoxin to Orchestrate Redox Homeostasis in Oral Squamous Cell Carcinoma.Research (Washington, D.C.) · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- SH2B3 Promotes PD-L1-Mediated Immune Evasion in Glioblastoma via BRCC3-Dependent IGF2BP2 Stabilization.International journal of biological sciences · 2026Article
- Hypoxia-induced secretory autophagy in cancer-associated fibroblasts promotes ECM remodelling through serglycin secretion in oral squamous cell carcinoma.Clinical and translational medicine · 2025Article
- Hsa-miR-423-5p selectively loaded in hypoxic exosomes reduces the sensitivity of normoxic hepatocellular carcinoma to sorafenib via autophagy.Cancer cell international · 2025Article
- Single-cell and spatial transcriptomics reveal lactylation-associated tumor cell clusters and define a prognostic risk model in glioblastoma.BMC cancer · 2025Article
- Non-Histone Lysine Modifications in Tumor Microenvironment: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
45 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the treatment of brain tumors by targeting kinase-regulated macroautophagy/autophagy, is under investigation, the precise mechanism underlying autophagy initiation and its significance in glioblastoma (GBM) remains to be defined. Here, we report that PAK1 (p21 [RAC1] activated kinase 1) is significantly upregulated and promotes GBM development. The Cancer Genome Atlas analysis suggests that the oncogenic role of PAK1 in GBM is mainly associated with autophagy. Subsequent experiments demonstrate that PAK1 indeed serves as a positive modulator for hypoxia-induced autophagy in GBM. Mechanistically, hypoxia induces ELP3-mediated PAK1 acetylation at K420, which suppresses the dimerization of PAK1 and enhances its activity, thereby leading to subsequent PAK1-mediated ATG5 (autophagy related 5) phosphorylation at the T101 residue. This event not only protects ATG5 from ubiquitination-dependent degradation but also increases the affinity between the ATG12-ATG5 complex and ATG16L1 (autophagy related 16 like 1). Consequently, ELP3-dependent PAK1 (K420) acetylation and PAK1-mediated ATG5 (T101) phosphorylation are required for hypoxia-induced autophagy and brain tumorigenesis by promoting autophagosome formation. Silencing
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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.