SQSTM1 Antibody
- Known as:
- SQSTM1 Antibody
- Catalog number:
- 5449
- Product Quantity:
- 0.5 mg
- Category:
- -
- Supplier:
- Prosci
- 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
- Downregulation of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been implicated in autophagic cell death. However, how ENPP1 regulates the interplay between autophagy and ferroptosis to maintain trophoblast homeostasis in the context of gestational diabetes mellitus (GDM) remains unclear. To determine ENPP1's role in autophagy-dependent ferroptosis and its contribution to GDM-related placental injury, clinical placental tissues, hyperglycemia-treated HTR8/SVneo trophoblasts, and streptozotocin-induced GDM mice were analyzed. Ubiquitination assays, co-immunoprecipitation, functional studies, and therapeutic interventions were conducted. ENPP1 was significantly reduced in GDM placentas and correlated with increased ferroptosis and lipid peroxidation. Mechanistically, ENPP1 recruited USP2 (ubiquitin-specific peptidase 2) to inhibit the ubiquitination and autophagic degradation of SQSTM1 (sequestosome 1), thereby enhancing its stability. ENPP1 loss promoted NCOA4-mediated ferritinophagy, leading to iron overload and ferroptosis. Restoring ENPP1 or inhibiting autophagy alleviated placental thinning and fetal growth restriction in GDM mice. ENPP1 regulates autophagy-dependent ferroptosis via the USP2-SQSTM1 axis, and its deficiency contributes to placental dysfunction. - Source: PubMed
Xu YahuiZhong GuangleiCheng XianghongYan JunZhou YanFeng YanFan Rujia - Cardiovascular disease is the leading cause of death worldwide. Disrupted protein homeostasis contributes significantly to cardiomyocyte dysfunction and loss. While autophagy is recognized as a critical cardioprotective mechanism, most therapeutic strategies have targeted overall autophagic flux, assuming that increasing degradative capacity is inherently beneficial. This approach overlooks a fundamental question: when multiple substrates compete for limited autophagic capacity, what determines which cargo is prioritized? This review focuses on the selective autophagy adaptors (sequestosome 1 [p62/SQSTM1], neighbor of BRCA1 gene 1 [NBR1], Tax1-binding protein 1 [TAX1BP1], optineurin [OPTN], nuclear dot protein 52 kDa [NDP52], and Fab1, YOTB, Vac1, EEA1 domain, and coiled-coil domain containing 1 [FYCO1]) as the molecular machinery governing cargo selectivity. We synthesize evidence demonstrating that adult cardiomyocytes face a unique "triage problem": as post-mitotic cells with a massive proteome and high metabolic demands, they must continuously prioritize which damaged mitochondria, protein aggregates, or sarcomeric components to eliminate. We integrate findings from cardiac studies with mechanistic insights from other cell types to map adaptor function in the heart. We propose that targeting selective autophagy adaptors may offer therapeutic precision beyond global flux modulation, directing autophagic machinery toward the cargo most relevant to individual pathological contexts. Currently, FYCO1 overexpression remains the only adaptor-level intervention validated to rescue cardiac function in vivo, highlighting both proof-of-concept and substantial opportunity for further investigation. Understanding not just how much the heart degrades, but also what it chooses to degrade may open new avenues for treating heart failure and cardiomyopathies. - Source: PubMed
Publication date: 2026/06/25
Espitia-Corredor Jenaro AOlivares-Silva FranciscoAlanis-Cubillos ConstanzaDeng YingfengWang Zhao V - We applied the TempO-LINC® platform to generate single-cell transcriptomic (SCTr) profiles of ∼40,000 HepaRG cells exposed to etoposide, brefeldin A, cycloheximide, rotenone, tBHQ, troglitazone, and tunicamycin at three concentrations for 24 hours. SCTr enabled a detailed analysis of adaptive stress response pathways (SRPs), including the unfolded protein response (UPR), oxidative stress response (OSR), heat shock response (HSR), and DNA damage response (DDR). Troglitazone upregulated lipid metabolism genes () along with HSR and UPR activation, with co-expression of , and in subsets of cells. Brefeldin A and tunicamycin strongly induced UPR markers () in subsets of cells, with some also expressing apoptotic () and autophagic () genes, indicating diverse stress responses. Rotenone activated , and in a fraction of cells, accompanied by and mild UPR induction, reflecting heterogeneous mitochondrial stress responses. We scored individual cells using literature-derived SRP gene signatures to characterize overall stress phenotypes and clustered them using a generalized Jaccard metric. The clustering revealed five phenotypic groups spanning cell states associated with homeostasis, adaptive responses, terminal outcomes, autophagy, and apoptosis. By systematically analyzing the distributions of cells in different states across treatments, we visualized dynamic shifts in cellular subpopulations responding to chemicals, revealing early stress responses and potential transitions to cell death. Our findings suggest the utility of SCTr in decoding stress states that could provide possible insights into transitions between cellular adaptive and terminal transitions involved in toxicity. - Source: PubMed
Publication date: 2025/08/26
Shah ImranGallegos DavidRobinette BrianChambers Bryant AEastburn Dennis JBell Douglas ACampbell Michelle RMartos Suzanne NCamiolo SalvatoreWhite Kevin SMartin NicoleMontis GioeleMcComb JoelSeligmann BruceChorley Brian N - Accelerated CHRN/AChR/nicotinic acetylcholine receptor internalization induced by auto-antibodies impairs neuromuscular junction transmission and contributes to myasthenia gravis (MG), a typical autoimmune disease. Although CHRN internalization is well established in MG pathogenesis, the downstream cellular events, especially those related to autophagy, remain poorly described. Here, we report that RAPSN/rapsyn, an intracellular CHRN-binding protein essential for its clustering, accumulates as aggregates in experimental autoimmune myasthenia gravis (EAMG) mice. In CHRN antibody-treated myotubes, RAPSN dissociates from internalized CHRN and forms aggregates due to exposure of its hydrophobic domains. These aggregates in turn impair the trafficking and membrane incorporation of newly synthesized CHRN, thereby exacerbating CHRN loss. Notably, the accumulation of RAPSN aggregates facilitates formation of HSPA/HSP70-BAG3 complex, which recognizes and transports the aggregates along microtubules to form perinuclear aggresomes for subsequent lysosomal degradation. Accordingly, pharmacological inhibition or knockdown of HSPA-BAG3 complex increases RAPSN aggregation, which participates in enhanced CHRN loss and worsened muscle weakness in EAMG mice. This study identifies HSPA-BAG3 aggrephagy as a protective mechanism that clears RAPSN aggregates to maintain CHRN integrity and suggests a potential therapeutic strategy for MG. 3-MA: 3-methyladenine; AAV: adeno-associated virus; CASA: chaperone-assisted selective autophagy; CHRN/nicotinic acetylcholine receptor: cholinergic receptor nicotinic; CHRN-ab: CHRN antibodies; CHX: cycloheximide; CMAP: compound muscle action potential; CQ: chloroquine; EAMG: experimental autoimmune myasthenia gravis; ER: endoplasmic reticulum; GAS: gastrocnemius; MAP1LC3A/B: microtubule associated protein 1 light chain 3 alpha/beta; MG: myasthenia gravis; NMJ: neuromuscular junction; Rapa: rapamycin; RAPSN/rapsyn: receptor associated protein of the synapse; SQSTM1: sequestosome 1; TA: tibialis anterior; αBTX-A594: α-bungarotoxin-Alexa-594. - Source: PubMed
Publication date: 2026/06/28
Liu YujiaXia GuofangShi HuaiyingZhu SimengLi HailongShi YifanOuyang WanlingXu CongfengDu Ailian - The targeted, substrate-specific degradation of paternal mitochondria inside the zygote, known as post-fertilization sperm mitophagy, is a crucial and evolutionarily conserved early embryonic event. It ensures the exclusive maternal inheritance of the mitochondrial genome. Post-fertilization sperm mitophagy was initially thought to only be achieved via the ubiquitin-proteasome system. Until pro-autophagic receptor proteins such as SQSTM1, GABARAP, as well as the proteasome-interacting ubiquitinated protein dislocase VCP, were identified as contributors to the degradation of the sperm mitochondria early after mammalian fertilization. This synergy of proteasomal and autophagic pathways ensures a timely degradation of sperm mitochondria shortly after fertilization. The discovery of these autophagic receptors lead researchers to believe there might be other autophagic receptors and determinants necessary for proper post-fertilization sperm mitophagy. Based on the established inventory of proteins from mass spectrometry trials of boar spermatozoa exposed to porcine oocyte extracts in an intra-specific porcine cell-free system (CFS), five candidate mitophagy determinants were further investigated in this study, namely LACTB, PRDX3, PSMA8, TOMM34, and FUNDC1. These proteins of interest were studied and validated by using in vitro fertilization (IVF) protocols, cell imaging of spermatids, spermatozoa, oocytes and zygotes, protein interactome analysis, and the porcine CFS. The proteins PSMA8 and TOMM34 behaved in accordance with our proteomic study predictions. The PSMA8 labeling increased after exposure to CFS; in agreement with the classification PSMA8 was given from the mass spectrometry findings. TOMM34 underwent a visible decrease in labeling after exposure to CFS, which also agreed with its proteomic classification; this labeling persisted in IVF zygotes. Except for LACTB, the examined proteins showed mutual interactions as well as interactions with previously identified sperm mitophagy factors in the STRING interactome analysis. Results from this study validate the novel porcine CFS as a valuable tool for the exploration of early fertilization events at a molecular level. Future phenotyping and functional studies using porcine CFS will advance the understanding of mitochondrial inheritance and zygotic development and potentially shed light on the origins of certain mitochondrial diseases arising from the failure of post-fertilization sperm mitophagy. - Source: PubMed
Publication date: 2026/06/29
Jones AlexisZelenková NatálieMantle EricaGardner ChloeKlusáčková BarboraZuidema DalenSutovsky MiriamPostlerová PavlaZigo MichalSutovsky Peter