Ask about this productRelated genes to: VPS4B Blocking Peptide
- Gene:
- VPS4B NIH gene
- Name:
- vacuolar protein sorting 4 homolog B
- Previous symbol:
- SKD1
- Synonyms:
- VPS4-2, SKD1B
- Chromosome:
- 18q21.33
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-22
- Date modifiied:
- 2016-04-05
Related products to: VPS4B Blocking Peptide
Related articles to: VPS4B Blocking Peptide
- The AAA+ ATPase VPS4 drives the ESCRT machinery in diverse intracellular membrane remodeling events, including endocytic receptor sorting, membrane repair, and autophagosome closure. Tumor cells often lose one VPS4 paralog (VPS4A or VPS4B), making them dependent on the remaining enzyme and creating a potential therapeutic vulnerability. Inhibiting VPS4 induces cancer cell-autonomous death and may also modulate the immune microenvironment, although the underlying mechanisms remain unclear. Here, we report that VPS4 inhibition triggered upregulation of cytokine and innate immune signaling, along with canonical NF-κB, stress response, and cell death pathways in murine rhabdomyosarcoma (RMS) cells. Pharmacological and genetic analyses identified the cGAS-STING-TBK1-IRF3 axis, activated by cytoplasmic mitochondrial DNA, as the primary driver of cytokine induction. In an orthotopic syngeneic RMS model, VPS4 inhibition suppressed tumor growth while fostering a more immunogenic microenvironment. Although STING was dispensable for VPS4 inhibition-induced RMS cell death, its loss reduced natural killer and dendritic cell infiltration and attenuated the overall anti-tumor effects of VPS4 inhibition. These findings establish a dual role for VPS4 inhibition in inducing tumor cell death and promoting anti-tumor immunity, highlighting the therapeutic potential of targeting VPS4 vulnerability in cancer. - Source: PubMed
Publication date: 2026/04/24
Zhang RayChen LongguiLiang XinwenZhang JiawenHamamoto KoutaHattori TatsuyaVangala VenugopalSchell Todd DSaulnier Sholler GiselleTakahashi YoshinoriWang Hong-Gang - Vacuolar protein sorting 4 (VPS4) is an AAA-ATPase that mediates ESCRT-III disassembly critical for membrane remodeling events like autophagosome closure and endolysosomal repair. Aberrant expression of VPS4 is associated with cancer progression and poor prognosis, making VPS4 a potential anticancer target. To date, very few VPS4 inhibitors have been reported, therefore the identification and development of VPS4 inhibitors is urgently needed. In this study, we employed a multi-tiered structure based virtual screening strategy, molecular dynamic simulation accompanied by pharmacokinetic analysis and in vitro screening to identify novel inhibitors of VPS4. The identified inhibitor comp-23 effectively inhibited the enzymatic activity of VPS4B with an IC value of 12.84 ± 2.51 µM. Protein ligand interaction profile and molecular dynamic simulation revealed the ATP binding residues such as Ala137, Gly177, Glu179, Asn279, and His313 were the main contributors to the binding of this compound. Comp-23 serves as a hit compound for further optimization to explore VPS4-related functions. - Source: PubMed
Publication date: 2025/11/25
Samad AbdusKhamis Mussa YussufJin PengToor Muhammad NaeemYu YinglanLuo LeiShao Hao - Multiple sclerosis (MS) is a chronic neuroinflammatory disease that progresses to a stage marked by irreversible neurological decline and widespread neurodegeneration. Necroptosis, a regulated form of cell death primarily triggered by tumor necrosis factor (TNF), has been implicated in neuronal loss in progressive MS. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery, essential for plasma membrane repair and vesicle trafficking, is known to counteract necroptosis in non-neural cells. In this study, we investigated whether ESCRT dysfunction contributes to neurodegeneration in the MS cortex. We identified a significant dysregulation of ESCRT-III complex components, particularly VPS4B and CHMP2A, in neurons of MS cortical grey matter. This dysregulation correlated with reduced neuronal density and increased meningeal inflammation. Notably, both demyelinated and normal-appearing grey matter showed decreased VPS4B, while CHMP2A loss was more restricted to areas of demyelination. These findings suggest that impaired ESCRT-III function may increase neuronal vulnerability to necroptosis and contribute to disease progression in MS. Our results highlight a novel pathway linking neuroinflammation, ESCRT dysfunction, and neuronal death, with potential therapeutic implications for neuroprotection in progressive MS. - Source: PubMed
Publication date: 2025/07/24
Picon CarmenAleksynas RobertasWojewska Marcelinade Virgiliis FrancescoMerkler DoronReynolds Richard - The endosomal sorting complex required for transport (ESCRT) is a multicomplex machinery comprising proteins that are conserved from bacteria to humans and has diverse roles in regulating the dynamics of cellular membranes. ESCRT functions have far-reaching consequences for cell biological processes such as intracellular traffic, membrane repair, cell signalling, metabolic regulation, cell division and genome maintenance. Here we review recent insights that emphasize the pathophysiological consequences of ESCRT dysfunctions, including infections, immune disorders, cancers and neurological diseases. We highlight the possibilities of using our knowledge about ESCRT structures and functions for drug discovery. - Source: PubMed
Publication date: 2025/06/25
Hurley James HCoyne Alyssa NMiączyńska MartaStenmark Harald - The tumor microenvironment (TME) supplies critical metabolites that support cancer cell survival and progression. Adipocytes support tumor progression by secreting free fatty acids (FFAs) and adipokines; however, the role and mechanisms underlying lipid droplet (LD) release from adipocytes remain elusive. - Source: PubMed
Publication date: 2025/05/23
Yin HaimengShan YingZhu QinYuan LingJu FengShi YuHan YumoWu RuiXia TianZhang KaiwenYou YiwenYou Bo