SQSTM1 Pre-design Chimera RNAi
- Known as:
- SQSTM1 Pre-design Chimera RNAi
- Catalog number:
- H00008878-R01
- Product Quantity:
- 10 nmol
- Category:
- -
- Supplier:
- Abno
- Gene target:
- SQSTM1 Pre-design Chimera RNAi
Related genes to: SQSTM1 Pre-design Chimera RNAi
- 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 Pre-design Chimera RNAi
Related articles to: SQSTM1 Pre-design Chimera RNAi
- The incidence of inflammatory bowel disease (IBD) has been demonstrated to be increased over recent decades. Butyrate derived from the gut microbiota is known to be beneficial in alleviating inflammation, yet the underlying mechanisms remain undefined. - Source: PubMed
Publication date: 2026/06/17
Mao QingyiLin BeibeiZhang WenluoZhang YuLei YueZhang ZhouXu Mengque - To investigate the mechanism by which SHP2 influences ferroptosis through the regulation of signaling pathways, thereby impacting hepatocellular carcinoma. Integrate bulk RNA-seq and single-cell transcriptomic data to identify differentially expressed genes and analyze cellular heterogeneity, pseudotemporal trajectories, and cell-cell communication networks. In vitro experiments involved treating HepG2, Huh7, and Hep3B cells with the SHP2 inhibitor (PHPS1), the CREB agonist (AE-18), the EZH2 inhibitor (IN-14), and the FOXO1 inhibitor (AS1842856). Western blot analysis was performed for P-SHP2, P-PI3K, nuclear P-CREB, nuclear EZH2, nuclear FOXO1, GPX4, Nur77, NCOA4, LC-3B, and SQSTM1; immunofluorescence was used to detect the localization and intensity of nuclear FOXO1 and nuclear CREB; biochemical colorimetric assays were used to measure Fe⁺, ROS, and oxidative stress markers; flow cytometry was used to detect apoptosis; CCK-8 assay for proliferation; Scratch and Transwell assays for migration and invasion. SHP2 resists ferroptosis in hepatocellular carcinoma by regulating the CREB/EZH2/FOXO1 signaling pathway, thereby modulating the protein expression of autophagy/NCOA4/GPX4. Integrated bulk RNA-seq and single-cell transcriptomic analyses further revealed that SHP2-mediated transcriptional reprogramming and altered cellular communication within the HCC microenvironment jointly promote resistance to ferroptosis. - Source: PubMed
Publication date: 2026/07/01
Yu GuodongHan JijingKang RanYang JihongCui Yong - SQSTM1 is one of the causative genes of neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The SQSTM1 protein regulates the degradation of polyubiquitinated proteins and autophagosome formation through its interaction with microtubule-associated protein light chain 3 (MAP1LC3/LC3). However, the molecular mechanisms by which SQSTM1-LC3 binding regulates the autophagy-endolysosomal system (APELS) remain unclear. To elucidate the spatiotemporal role of SQSTM1, we transiently expressed wild-type SQSTM1 or missense mutants carrying mutations in the LC3-interacting region (LIR), fused with the photoconvertible fluorescent protein Dendra2. Live-cell fluorescence imaging and co-localization analyses with markers of the APELS were then performed. Particle analysis of photoconverted or non-photoconverted SQSTM1-positive structures in live cells revealed that the pathogenic L341V variant formed larger structures than the wild-type. Co-localization analyses further showed that both the L341V and artificial LIR3A mutants accumulated in large ubiquitin-positive structures, likely due to impaired localization to autophagosomes. These results suggest that mutations within the LIR differentially affect autophagosome formation and cargo degradation within APELS-related compartments, highlighting the importance of SQSTM1 structural integrity in ALS/FTD pathogenesis. - Source: PubMed
Shimakura KentoOka AkiraYudahira HarukaHama YutaroOtomo AsakoHadano Shinji - Macroautophagy/autophagy, a conserved intracellular catabolic pathway, removes deleterious cytosolic material to maintain homeostasis and survival. Upon autophagy induction, a unique double-membraned structure, the phagophore, forms and engulfs cytosolic material, the cargo, as it closes to become an autophagosome. Mammalian Atg8-family proteins (ATG8s) are ubiquitin-like proteins which are essential for engulfment of the cargo and membrane closure. ATG8s are recruited to the phagophore by ATG12-ATG5-ATG16L1, an E3-like ligase which is recruited by PtdIns3P-binding WIPI proteins. Covalent lipidation of the ATG8s to phosphatidylethanolamine by the E3 ligase occurs specifically on the phagophore membrane allowing recruitment of cytosolic cargo and cargo receptors, such as SQSTM1/p62. While ATG8-cargo receptor interactions are well established, how the ATG8s bind cargo and cargo receptors on the inner membrane of the phagophore has not been studied. To recapitulate these events, we use giant unilamellar vesicles (GUVs) and encapsulate protein machinery and cargo, generating a membrane platform to which ATG8 proteins can be recruited. Inside the GUVs we reconstituted WIPI2B-directed and cargo-directed ATG8 lipidation revealing distinct roles of WIPI2B and SQSTM1 in initiating ATG8 conjugation. We show that SQSTM1 and SQSTM1 droplets are recruited to the GUV inner membrane through interaction with membrane bound ATG8s. Through the development of a bead-based membrane deformation assay, we show redistribution and local enrichment of membrane-bound ATG8s occurs upon binding to SQSTM1 droplets. Our work demonstrates fundamental molecular mechanisms into phagophore-ATG8-cargo interactions providing novel model systems to investigate ATG8-cargo interactions on the inner phagophore membrane.:ATG: autophagy related; cDICE: continuous droplet interface crossing encapsulation; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; GABARAP: GABA type A receptor-associated protein; GUV: giant unilamellar vesicle; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; LIR: LC3-interacting region; LUV: large unilamellar vesicle; NBD: 7-nitrobenz-2-oxa-1,3-diazol-4-yl; PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; PolyUb: K63-linked polyubiquitin; POPC: 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine; POPE: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine; Rh-PE: 18:1 Liss Rhod PE; SQSTM1/p62: sequestosome 1; WIPI2B: WD repeat domain, phosphoinositide interacting 2B. - Source: PubMed
Publication date: 2026/06/30
Zhang WenxinLitschel ThomasSchreiber AnneD'Antuono RoccoTooze Sharon A - 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