GABARAP (GABA Type A Receptor-Associated Protein)

Functionally, GABARAP depletion disrupted mitophagy flux, mitochondrial integrity, and energy production, thereby impairing osteosarcoma cell proliferation and migration. These findings reveal that GABARAP links mitophagy-driven metabolic adaptation with immune evasion, representing a key regulator and potential therapeutic target in osteosarcoma.

These findings establish G2E3 as a novel ubiquitin-related regulator of autophagy, specifically facilitating autophagosome-lysosome fusion via a GABARAPs-dependent mechanism. This study reveals a previously unrecognized role of G2E3 in late-stage autophagy and suggests that targeting G2E3 could provide a potential therapeutic approach for modulating autophagy-dependent cellular processes, including cancer progression.

Manipulation of plasma membrane PS content, PS binding by Rubicon or the PS-clustering domains of receptors prevents LAP and delays phagosome maturation. Therefore, the initiation of LAP represents a novel mechanism of PS-mediated signal transduction following ligation of surface receptors.

These alterations included activation of the cholesterol biosynthesis pathway and changes in the distribution of key lipid classes, such as phospholipids, ceramides and triglycerides. Further mechanistic studies indicated that 5d and 5j triggered an ER stress response and may impair lysosomal function, as suggested by the accumulation of pro-cathepsin D. Collectively, these findings demonstrate that 5j is a novel and potent late-stage autophagy inhibitor with a distinct mechanism of action compared to currently available inhibitors.

This review offers an in-depth analysis of FAM134B's structure, function, and regulation, emphasizing its role in infectious diseases, neuropathies, cancer, metabolic disorders, degenerative conditions, and cardiovascular diseases. The evidence presented highlights the need for further research on FAM134B as a potential therapeutic target in human diseases.

We also discussed the possible role of GABARAP in tumor progression through the regulation of autophagy. Additionally, this study suggest novel therapeutic approach targeting the GABAergic system in the treatment of tumors.

While YTHDF depletion induces cell death in contact-inhibition-deficient HCT116 cancer cells, contact-inhibited MRC5 and RPE1 cells remain unaffected. Our findings uncover a regulatory pathway that governs YTHDF protein stability with significant implications for cancer biology and cell fate determination and suggest the existence of an autophagy-mediated degradation pathway for m6A-modified RNA.

Finally, using the Genomics of Drug Sensitivity in Cancer and Cancer Therapeutics Response Portal databases, potential drugs [(5Z)-7-oxozeaenol, selumetinib, RDEA119, AZ628, dabrafenib and trametinib] were identified based on the aforementioned seven key carcinogenic genes, focusing on those that targeted multiple genes. In conclusion, the present study identified 14 key ferroptosis-related genes, and seven key carcinogenic genes, which represent promising novel molecular targets for the prognosis and treatment of GC.

The selective expression pattern of GABARAP genes in glioblastoma can be utilized to screen for patients who might respond better to temozolomide treatment. The differential expression of GABARAP family members highlights the subtle regulation of the autophagy pathway in response to environmental cues.

Importantly, elevated PI4KB phosphorylation at S256 and T263 was observed in RAS-mutated cancer cells and colorectal cancer specimens. Inhibition of PI4KB S256 and T263 phosphorylation led to a reduction in RINCAA activity and tumor growth in both xenograft and KPC models of pancreatic cancer, suggesting that targeting ULK1-mediated PI4KB phosphorylation could represent a promising therapeutic strategy for RAS-mutated cancers.

We highlight LIR-based probes and LC3/GABARAP-specific deconjugases as critical tools that allow precise tracking and manipulation of ATG8 in autophagic and non-autophagic contexts. These advancements hold therapeutic promise for treating autophagy-related diseases, including cancer and neurodegenerative disorders, by targeting ATG8-driven pathways that maintain cellular homeostasis.

Additionally, NAT10 impedes autophagy flux by preventing the fusion of autophagosomes with lysosomes and suppressing GABARAP transcription, which is regulated by EZH2-mediated H3K27me3. In summary, our study elucidates the biological significance and molecular mechanisms of the NAT10/SGK2/EZH2 axis in the pathogenesis of lung cancer, potentially providing novel prognostic markers and therapeutic targets for its treatment.