Sqstm1
- Known as:
- Sqstm1
- Catalog number:
- 065374A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Sqstm1
Related genes to: Sqstm1
- 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
Related articles to: Sqstm1
- 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 - Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer remains a pressing clinical challenge. Liquid-liquid phase separation has emerged as a new mechanism of drug resistance, yet its role in EGFR-TKI resistance in lung cancer is largely unexplored. Herein, we prioritized Sequestosome 1 (SQSTM1/p62) as a key condensate by integrating proteomics data from EGFR-TKI resistance cell lines and clinical biopsy specimens, in which the cytoplasmic p62 condensate formation positively correlated with EGFR-TKI resistance. Domain mapping demonstrated that the PB1 and UBA domains of p62 were critical for promoting phase separation and reducing sensitivity to EGFR-TKI treatment, whereas S403 phosphorylation promoted p62 condensation and EGFR-TKI resistance. Further xenograft studies validated that reduction of p62 condensation restores EGFR-TKI sensitivity. Kinase enrichment and interaction assays identified TBK1 as an upstream regulator of p62 S403 phosphorylation to promote p62 condensation after pharmacological inhibition of EGFR. Notably, among the five compounds identified from a drug library screen that both disrupted p62 condensate formation and inhibited the viability of resistant cells, the highly selective TBK1 inhibitor GSK8612 stood out. GSK8612 inhibited p62 S403 phosphorylation and consequently, at subcytotoxic doses, synergized with EGFR-TKIs to suppress the viability of resistant cells and tumor growth in the xenograft mouse model. These findings propose TBK1-p62 axis links p62 condensate homeostasis to EGFR-TKI resistance as an underlying mechanism of action and an emerging strategy to resensitize EGFR-TKI treatment in resistant lung cancer. - Source: PubMed
Publication date: 2026/06/26
Song YuexiaoShao ChangchunZhang YiruoYang MinLiu YaqianChen ShengGao JiaLi ZihuanLi BinYao XuebiaoLiu XingRuan KeDu Yingying - Primary pulmonary inflammatory myofibroblastic tumor (IMT) associated with paraneoplastic pemphigus (PNP) is extremely rare. IMT is an intermediate (rarely metastasizing) mesenchymal neoplasm rather than a conventional sarcoma. We report a case of a 68-year-old female patient who initially presented with generalized skin rash, oral mucosal ulceration, and fever. Chest CT revealed a thoracic mass (initially difficult to determine whether mediastinal or pulmonary in origin). Subsequent thoracotomy and surgical resection with pathological examination confirmed an ALK-rearranged inflammatory myofibroblastic tumor (SQSTM1: ALK fusion) of pulmonary origin. Oral mucosal pathology, combined with clinical findings, supported a diagnosis of PNP. This case aims to provide reference for the diagnosis and treatment of patients with primary pulmonary IMT complicated by PNP. However, the follow-up period was short and systemic immunosuppressive therapy was not administered; this should be regarded as a cautionary note rather than a therapeutic recommendation. - Source: PubMed
Publication date: 2026/06/10
Dong YiGuan YongjieFeng ShuangWang XiaoweiRen XiyuanGao Ke - Autophagy is a conserved catabolic process that degrades damaged proteins and organelles to preserve cellular homeostasis. Autophagy plays two opposing roles during viral infection. On the one hand, it can be subverted by viruses to facilitate replication and immune evasion. On the other hand, it limits viral infection by delivering viral components to lysosomes. The interaction between autophagy and important picornaviruses that infect cattle and poultry, such as SVV, EMCV, FMDV, and DHAV, is the main topic of this paper. However, comprehensive summaries focusing specifically on livestock and poultry remain limited. We summarize current research showing that these viruses evade host protection by manipulating several steps of the autophagic pathway, from initiation to lysosomal fusion, to produce replication-favorable environments. Notably, by directing the breakdown of viral capsid proteins, specific autophagy receptors such as SQSTM1/p62, NDP52, and optineurin (OPTN) serve as antiviral effectors. In response, picornaviruses have developed proteolytic strategies to inactivate these receptors, such as SVV 3C-mediated cleavage of SQSTM1 and OPTN. Moreover, different immune evasion tactics are shown by virus-specific engagement of organelle-selective autophagy, such as ER-phagy (SVV) or mitophagy (DHAV). The development of broad-spectrum antiviral treatments and autophagy-based biomarkers for livestock disease progression may benefit from an understanding of the convergent and different ways picornaviruses take advantage of the autophagic machinery. - Source: PubMed
Publication date: 2026/06/09
Ma HaibinLiu RongchangLiao Ming