Ask about this productRelated genes to: SQSTM1 antibody
- Gene:
- SQSTM1 NIH gene
- Name:
- sequestosome 1
- Previous symbol:
- PDB3, OSIL
- Synonyms:
- p62, p60, p62B, A170
- Chromosome:
- 5q35.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-06-13
- Date modifiied:
- 2019-03-07
Related products to: SQSTM1 antibody
Related articles to: SQSTM1 antibody
- Macroautophagy/autophagy serves as a crucial cellular defense mechanism against invading pathogens. However, viruses have evolved diverse strategies to evade or even exploit autophagy for their own replication. In this study, we reveal that the African swine fever virus (ASFV)-encoded I10L protein suppresses autophagy by blocking autophagosome-lysosome fusion. Mechanistically, I10L directly interacts with the endolysosomal RAB GTPase RAB7, a master regulator of vesicle docking at late endosomes and lysosomes. This interaction competitively prevents RAB7 from binding to VPS39, a core component of the homotypic fusion and vacuole protein sorting (HOPS) complex. Consequently, I10L disrupts the assembly of the STX17-SNAP29-VAMP8 SNARE complex, which is essential for autophagosome-lysosome fusion. ASFV infection thus induces autophagosome accumulation, whereas I10L deletion reverses this effect and attenuates viral replication in primary macrophages. Our findings uncover a novel immune evasion strategy by which ASFV subverts lysosomal degradation through RAB7-HOPS axis manipulation, providing both mechanistic insights into viral pathogenicity and potential therapeutic targets for antiviral development. ASFV: African swine fever virus; GEF: guanine nucleotide exchange factor; GFP: green fluorescent protein; HOPS: homotypic fusion and vacuole protein sorting; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PAMs: primary alveolar macrophages; RAB7: RAB7, member RAS oncogene family; siRNA: small interfering RNA; SNAP29: synaptosome associated protein 29; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TM: transmembrane domain; VAMP8: vesicle associated membrane protein 8; VPS39: VPS39 subunit of HOPS complex; VPS41: VPS41 subunit of HOPS complex; YKT6: YKT6 vesicular SNARE protein. - Source: PubMed
Publication date: 2026/05/15
Chen MengSunkang YongjieCheng TongLiu LeiLi HuananYuan HuajinHuang LihongSun LeiQi WenbaoShang Yingli - This study investigated the neuroprotective effects and mechanisms of poliumoside (POL) against ischemic stroke, focusing on oxidative stress and mitochondrial dysfunction. Using an Oxygen-Glucose Deprivation/Reperfusion (OGD/R) model in Neuro-2a cells and a photothrombotic stroke model in C57BL/6J mice, we demonstrated that POL treatment significantly improved post-injury outcomes. In mice, POL enhanced motor coordination and grip strength, reduced cerebral infarct volume, and alleviated neuronal damage and apoptosis. Crucially, it suppressed brain oxidative stress, as shown by decreased reactive oxygen species (ROS) levels. In OGD/R-injured Neuro-2a cells, POL dose-dependently increased cell viability, reduced ROS and apoptosis, and improved mitochondrial function by stabilizing membrane potential and attenuating calcium overload. Mechanistically, POL activated the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway antioxidant pathway, promoting Nrf2 nuclear translocation and upregulating downstream proteins Heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). It also modulated autophagy by affecting Microtubule-associated proteins 1A/1B light chain 3B (LC3B) and Sequestosome 1 (SQSTM1), and exerted anti-apoptotic effects by regulating B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). In conclusion, POL confers protection against ischemic injury primarily by mitigating oxidative stress and preserving mitochondrial integrity via activation of the Nrf2 pathway and regulation of associated cellular processes. - Source: PubMed
Publication date: 2026/05/13
Qin RuiHan Bo-WenTao Jing-YingJin Xian-ZhuZhang Wen-FangZhao Wen-LeFeng Wan-DiDu Guan-HuaWang Yue-Hua - Central to the pathogenesis of type 2 diabetes (T2D) is the failure in insulin secretion from pancreatic β-cells associated with insulin resistance. The nuclear receptor RXRA/RXRα (retinoid X receptor alpha) is a transcriptional regulator of insulin secretion and systemic glucose metabolism. Here, we show that the macroautophagic/autophagic receptor SQSTM1/p62 (sequestosome 1) sequesters RXRA for lysosomal degradation to modulate glucose metabolism and insulin secretion. Under glucolipotoxicity, RXRA is released from SQSTM1 to inhibit mitochondrial respiration and insulin secretion and to induce lipogenesis. SQSTM1-dependent degradation of RXRA was reconstituted and mice using ATB1002, a chemical N-degron designed to bind and activate SQSTM1 as an N-recognin of the N-degron pathway. In prediabetic and T2D models, SQSTM1 agonists induced the lysosomal degradation of RXRA, and enhanced glucose-stimulated insulin secretion and insulin responsiveness. These results identify SQSTM1 as a master regulator in glucose metabolism and insulin secretion, providing a therapeutic means to treat T2D. - Source: PubMed
Publication date: 2026/05/14
Jung Eui JungKim Hye YeonBae Tae HyunChoi Eun NamLim HyominKim MinjiMun Su RanLee Yoon JeeHahn SoojungLee Dong RyulPark Woo-JaeSuh Young HoKwon Yong TaeSon Yeon SungKim Hee-YeonPark Joo-Won - Proteasome inhibitor drugs are currently used in the clinic to treat multiple myeloma and mantle cell lymphoma. These inhibitors cause accumulation of undegraded proteins, thus inducing proteotoxic stress and consequent cell death. However, cancer cells counteract this effect by activating an adaptive response through the transcription factor nuclear factor erythroid 2-related factor 1 (NRF1, also known as NFE2L1). NRF1 induces transcriptional upregulation of proteasome and autophagy/lysosomal genes, thereby reducing proteotoxic stress and diminishing the effectiveness of proteasome inhibition. While suppressing this protective autophagy response is one potential strategy, here we investigated whether this heightened autophagy could instead be leveraged therapeutically. To this end, we designed an autophagy-targeting chimera (AUTAC) compound to selectively degrade the anti-apoptotic protein Mcl1 via the lysosome. Our results show that this lysosome-mediated targeted degradation is significantly amplified in the presence of proteasome inhibition, in a NRF1-dependent manner. Mechanistically, AUTAC-driven Mcl1 clearance requires K63-linked ubiquitination by UBC13 and TRAF6 and recognition by the cargo receptor p62/SQSTM1. The combination of the proteasome inhibitor carfilzomib and Mcl1 AUTAC synergistically promoted cell death in both in vitro models, including wild-type and proteasome inhibitor-resistant multiple myeloma and lung cancer cells, and in mouse tumor xenografts. Thus, our work offers a novel strategy for enhancing proteasome inhibitor efficacy by exploiting the adaptive autophagy response. More broadly, our study establishes a framework for amplifying lysosome-mediated targeted protein degradation, with potential applications in cancer therapeutics and beyond. - Source: PubMed
Publication date: 2026/05/11
Elshazly Ahmed MHosseini NayyerehalsadatVangala JanakiramShen ShanweiNeely VictoriaHu XiaoyanPagare Piyusha PHarada HisashiGrant StevenRadhakrishnan Senthil K - The prevalence of major depressive disorder (MDD) is increasing globally, particularly among adolescents. Although gut-brain axis dysfunction has been implicated in adolescent depression, the mechanisms by which gut microbiota dysbiosis drives depressive behaviors and potential antidepressant targets remain unclear. In this study, fecal microbiota transplantation (FMT) was performed from either healthy controls (HCs) or adolescents with MDD into antibiotic-treated adolescent rats. FMT from MDD adolescents induced depressive-like behaviors in recipient rats. Metagenomic sequencing revealed that FMT from MDD adolescents led to alterations in gut microbiota in recipient rats. While qPCR, Western blotting, immunofluorescence, and transmission electron microscopy (TEM) confirmed that these rats exhibited prefrontal cortex (PFC) autophagy hyperactivation, evidenced by a reduction in SQSTM1/p62 levels, an elevation in the LC3-II/LC3-I ratio, upregulated Beclin1, and increased numbers of autolysosomes. Similar autophagy-related transcriptional changes were observed in peripheral blood from MDD adolescents. Furthermore, ELISA showed reduced plasma lysine levels in MDD adolescents and decreased lysine concentrations in the PFC of FMT-MDD rats. The antidepressant effect of lysine and its interaction with autophagy were explored in a chronic unpredictable mild stress (CUMS) rat model with or without rapamycin (the autophagy activator, RAPA). Lysine supplementation alleviated depressive-like behaviors and suppressed PFC autophagy hyperactivation, while these effects were abolished by RAPA co-treatment. These findings reveal lysine deficiency as a metabolic bridge between gut microbiota imbalance and neuronal autophagy dysregulation, suggesting a gut microbiota-lysine-autophagy axis as an innovative mechanism and therapeutic focus for adolescent depression. - Source: PubMed
Publication date: 2026/05/11
Zhang JushuangChen FeiXu XiaoxiaZhang LigeZhang LumanQin BingjieLi KunyaoLiu QuanbingHou HanchenLi YaoLiu ChenxiLi YinanShi JiaqiTeng TengWang ChaoZhou Xinyu