SQSTM1 antibody
- Known as:
- SQSTM1 (anti-)
- Catalog number:
- orb137277
- Product Quantity:
- 50 ug
- Category:
- -
- Supplier:
- Biorb
- Gene target:
- SQSTM1 antibody
Related 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
- Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating pathogens affecting the global swine industry. Autophagy plays an important role in both host defense and PRRSV infection. However, the mechanisms by which the host exploits the autophagy pathway to antagonize PRRSV infection remain largely unknown. Here, we perform transcriptomic analysis of porcine alveolar macrophages isolated from PRRSV-infected piglets and reveal a significant upregulation of the mRNA levels for the E3 ubiquitin ligase IDOL. These findings are further validated by experiments. Functional studies reveal that IDOL acts as a host restriction factor for PRRSV: ectopic expression of IDOL markedly suppresses viral replication, while knockdown of endogenous IDOL enhances it. Mechanistically, IDOL catalyzes K63-linked polyubiquitination of the viral nonstructural protein 3 (Nsp3) at lysine 101 (K101) and recruits the selective autophagy receptor SQSTM1, thereby targeting Nsp3 for degradation via the autophagy-lysosomal pathway and effectively suppressing viral replication. Notably, the ubiquitin-associated and LC3-interacting region domains of SQSTM1 are essential for this autophagic clearance of Nsp3. Furthermore, using a reverse genetics approach, we generate an Nsp3 K101R mutant virus and confirm that this specific mutation enables the virus to evade IDOL-mediated Nsp3 degradation, thereby restoring its replication competence. In summary, we uncover an autophagy-dependent antiviral mechanism, establish IDOL as an innate immune regulator with a non-canonical function, and define a viral immune evasion strategy, positioning IDOL as a promising therapeutic target for PRRSV control.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) represents a major threat to global swine production, inflicting substantial economic damage and endangering food security. Here, we identify the E3 ubiquitin ligase IDOL as a critical host restriction factor that combats PRRSV through a previously unrecognized autophagy-mediated mechanism. We demonstrate that PRRSV infection robustly upregulates the transcription factor ZNF460, which directly drives IDOL expression. During PRRSV infection, IDOL drives the autophagic degradation of Nsp3 by catalyzing its K63-linked ubiquitination at lysine 101 and engaging the selective autophagy receptor SQSTM1, triggering a potent antiviral response. Using reverse genetics, we generate an Nsp3 K101R mutant virus and demonstrate that this mutation enables the virus to escape IDOL-mediated degradation and restore replication competence, providing genetic validation of this antiviral axis. Collectively, our findings establish an autophagy-dependent antiviral mechanism, define IDOL as an intrinsic immune regulator with a previously unrecognized function, and elucidate a precise viral immune evasion strategy, thereby positioning IDOL as a promising therapeutic target for PRRSV intervention. - Source: PubMed
Publication date: 2026/09/15
Yan JiecongWu YuhanXu HuiruiLai PengningHuang LingHe ZhanXie YongshengGuo Chunhe - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by poor prognosis and limited response to gemcitabine, the standard first-line chemotherapy. One major contributor to chemoresistance is autophagy, a process frequently upregulated in PDAC. In this study, we examined the ability of type I interferons (IFNα2b and IFNβ1a) to modulate autophagy and disturb tumor cell resistance to gemcitabine. PDAC cells were treated with increasing concentrations of IFNα2b or IFNβ1a, and cell proliferation was assessed by [H]-thymidine incorporation. Apoptosis was evaluated by TUNEL staining following treatments with interferons and/or gemcitabine. STAT1 phosphorylation was analyzed as a marker of downstream type I interferon signaling. Autophagy was analyzed by western blot for LC3B, Beclin-1, Bcl-XL and p62/SQSTM1, and by quantifying autophagic flux using mCherry-EGFP-LC3B-transfected cells in the presence or absence of lysosomal inhibitors. We found that IFNα2b promoted autophagic flux and reduced gemcitabine-induced cell death, indicating a cytoprotective role. In contrast, IFNβ1a reduced autophagosome formation and significantly enhanced cell death, without clear evidence of altering autophagic flux. Both interferons induced STAT1 phosphorylation, confirming engagement of downstream type I interferon signaling. Our findings highlight the contrasting roles of IFNα2b and IFNβ1a in the regulation of autophagy and gemcitabine response and suggest that IFNβ1a, by reducing autophagosome formation, may sensitize PDAC cells to chemotherapy. These findings identify IFNβ1a as a potential chemosensitizing agent in PDAC and provide a rationale for further evaluating combinations of IFNβ1a, gemcitabine, and autophagy-targeting strategies to overcome chemoresistance. - Source: PubMed
Publication date: 2026/09/15
Bonilla Lucy ELedesma Martín MBehr Santiago APibuel Matías APalanek María LGrasso Daniel HGarcia Maria NGarona JuanLompardía Silvina LÁlvarez ElidaPapademetrio Daniela L - Persistently poor glioblastoma (GBM) survival necessitates better elucidation of tumor drug responses. After observing that low curcumin and all-trans retinoic acid (ATRA) doses stimulated cell proliferation and counteracted each other's high-dose antiproliferative effects in U87 GBM cells, drug influences on cell growth, migration, and death and the antiproliferative interaction proteome were further studied. Cell proliferation and migration were assessed by xCELLigence Real-Time Cell Analysis (RTCA). Cell death was defined using flow cytometry. Drug interactions were determined with CompuSyn software (version 1.0). Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), High-Performance Liquid Chromatography (HPLC), and SequestHT software (version 1.4) were utilized for peptide generation and identification. ATRA at high doses inhibited cell growth and migration more efficiently. Curcumin was more proliferative and antagonistic against anti-growth effects at low doses. Migration inhibition and apoptosis occurred synergistically at the highest drug doses. ATRA influenced the proteome more remarkably, reducing Transforming Growth Factor Beta Induced (TGFBI), Phosphoglycerate Dehydrogenase (PHGDH), tenascin, and Sequestosome 1 (SQSTM1). These effects were alleviated by curcumin, except for SQSTM1. Uveal Autoantigen With Coiled-Coil Domains And Ankyrin Repeats (UACA) and Sad1 And UNC84 Domain Containing 2 (SUN2) were increased by ATRA and curcumin, and to a lesser extent by the combination. Hexokinase 2 (HXK2) was increased by curcumin and the combination. Heme Oxygenase 1 (HMOX1) was depleted by the combination, but not by the single agents. SQSTM1 and HMOX1 reductions may mediate anticancer synergism, while the remaining changes may indicate ongoing hormetic pathways not reflected in cell counts. - Source: PubMed
Publication date: 2026/08/31
Sönmez CeydaAltinoz Meric ABaltacıoğlu AleynaErgün BüşraÖzpınar Aysel - Puerarin (Pue), a major isoflavone derived from , has demonstrated neuroprotective potential in multiple neurological disorders; however, its effects on ethanol (EtOH)-induced cortical injury and the associated molecular responses remain incompletely understood. In the present study, network pharmacology was combined with in vivo and in vitro experiments to investigate molecular responses associated with the effects of Pue on EtOH-induced neurotoxicity. Public databases were used to predict targets of Pue and alcohol-related brain injury, followed by protein-protein interaction analysis, Gene Ontology annotation, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A total of 101 overlapping targets were identified, among which TNF, AKT1, EGFR, TP53, and PPARG emerged as major hub targets, and PI3K-Akt signaling pathway was among the pathways that remained significantly enriched after FDR correction. In a 4-day binge EtOH rat model, Pue attenuated EtOH-associated increases in oxidative stress, neuronal degeneration, and apoptotic markers in cortical tissue. This was accompanied by attenuation of the EtOH-associated reductions in the p-AKT/AKT and p-mTOR/mTOR ratios, as well as an attenuation of EtOH-associated changes in LC3, ATG5, and Beclin-1 expression. In primary cortical neurons, Pue partially attenuated the EtOH-associated loss of neuronal viability and preserved neurite morphology. Bafilomycin A1 (BafA1)-based analysis of LC3-II and p62/SQSTM1 showed an overall BafA1-sensitive increase in LC3-II without a significant treatment-dependent difference in the BafA1 response. Collectively, these findings suggest that Pue attenuates binge EtOH-induced cortical neurotoxicity in association with changes in AKT/mTOR phosphorylation and autophagy-related responses. - Source: PubMed
Publication date: 2026/09/14
Liu FuHuang ShuyingXiao HongwenZhou YuhongLin LongLiu ZaiqiangLan JumeiChen XiaohongTian Hua - Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, for which radiotherapy constitutes the key component of standard comprehensive treatment; however, tumor relapse could inevitably arise from intrinsically radioresistant GBM subclones. Radiotherapy exerts biphasic regulatory effects on the tumor immune microenvironment (TIME), with transient activation followed by sustained immunosuppression. Nevertheless, it remains elusive how radioresistant GBM cells remodel such an immunosuppressive TIME to evade immune surveillance. Herein, integrative analyses encompassing clinical specimens, public single-cell RNA-seq datasets, orthotopic glioma models, primary CD8 T cell co-culture systems, and tandem mass tag (TMT) proteomics indicated that CD81 was highly expressed in radioresistant GBM and governed GBM immune evasion. CD81-high tumor cells were surrounded by functionally exhausted CD8 T cells, alongside immunosuppressive signature within neighboring myeloid and NK cells. CD81 depletion promoted selective macroautophagic/autophagic degradation of CD274/PD-L1, increased CD8 T cell infiltration and cytotoxic activity, reduced M2-like tumor-associated macrophages, and suppressed intracranial tumor growth. Moreover, CD81-knockdown augmented the antitumor efficacy of anti-PDCD1/PD-1, yielding a pronounced survival benefit when combined with radiotherapy. Mechanistically, CD81 interacted with CD274 via its large extracellular loop (LEL) and recruited the deubiquitinase USP14 through its cytoplasmic C-terminal tail (CCT). This resultant ternary complex erased K63-linked ubiquitination at the K280 residue of CD274, thereby abolishing SQSTM1/p62-dependent recognition and subsequent autophagy-lysosomal degradation of CD274 to maintain its protein stability. Collectively, our work establishes CD81 as a pivotal bridge connecting radioresistance to immune escape via sustaining CD274 abundance in GBM, highlighting CD81 as a promising therapeutic target to optimize radioimmunotherapy. - Source: PubMed
Publication date: 2026/09/13
Zeng LiangZhou YuchuanCai LinboZheng WangLiu XinglongLiao WeiXiao YuqiJin XiaoyaZhang JialingLai MingyaoLi HainanXu YanwuZhang JianghongPan YanWang YangShao Chunlin