SQSTM1 (Phospho S207)
- Known as:
- SQSTM1 (Phospho S207)
- Catalog number:
- AP3801a-ev20
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- SQSTM1 (Phospho S207)
Related genes to: SQSTM1 (Phospho S207)
- Gene:
- RNA5SP207 NIH gene
- Name:
- RNA, 5S ribosomal pseudogene 207
- Previous symbol:
- RN5S207
- Synonyms:
- -
- Chromosome:
- 6p21.1
- Locus Type:
- pseudogene
- Date approved:
- 2011-11-04
- Date modifiied:
- 2014-11-19
- 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 (Phospho S207)
Related articles to: SQSTM1 (Phospho S207)
- Abdominal aortic aneurysm (AAA) remains a life-threatening vascular disease without effective pharmacologic therapy. Although 3-hydroxyanthranilic acid (3HAA), a kynurenine-pathway metabolite with dual redox effects, has been implicated in vascular diseases. How 3HAA instigates AAA is poorly defined. - Source: PubMed
Publication date: 2026/06/12
Ramprasath TharmarajanHan Young-MinDing YeCarr Sean MichaelZou Ming-Hui - Endothelial dysfunction is a critical determinant of sepsis-associated organ injury, often driven by its interaction with overactivated immune cells. Neutrophils, the dominant early responders in sepsis, contribute to endothelial barrier disruption, yet the underlying metabolic and epigenetic mechanisms remain poorly understood. Here, we observed elevated intracellular lactate levels in neutrophils from septic patients which correlated with organ dysfunction and systemic inflammatory markers. Mechanistically, lactate-induced histone H3K18 lactylation (H3K18la) enhanced (autophagy related 7) transcription, initiating a non-degradative, secretory autophagy program. This facilitated the extracellular release of IL1B/IL-1B (interleukin 1 beta), a key driver of endothelial dysfunction. Interference of lactate production, ATG7 expression or IL1B signaling alleviated endothelial dysfunction . , myeloid-specific deletion of the lactylation writer EP300/p300 (EP300 lysine acetyltransferase) mitigated pulmonary endothelial dysfunction and lung injury. Additionally, the stress-responsive transcription factor ATF4/CREB-2 (activating transcription factor 4) was found to directly interact with both EP300 and H3K18la, amplifying H3K18la-driven transcription. Our findings uncover a metabolically driven, epigenetically regulated secretory autophagy pathway in neutrophils that mediates endothelial dysfunction. Our study provides mechanistic insights into neutrophil-endothelial crosstalk in sepsis and identifies EP300, ATG7, and IL1B as potential therapeutic targets for sepsis. ALI: acute lung injury; ANOVA: analysis of variance; ATF4/CREB-2: activating transcription factor 4; ATG7/GSA7: autophagy related 7; ATP: adenosine triphosphate; BafA1: bafilomycin A; BMDN: bone marrow-derived neutrophil; C-CASP1: cleaved-caspase 1; CDH5/CD144: cadherin 5; CRP/PTX1: C-reactive protein; CST3: cystatin C; CXCL8/IL-8: C-X-C motif chemokine ligand 8; DAPI: 4',6-diamidino-2-phenylindole; DEG: differentially expressed gene; dHL-60: dimethyl sulfoxide-differentiated HL-60 cell; DMSO: dimethyl sulfoxide; ELISA: enzyme-linked immunosorbent assay; EP300/p300: EP300 lysine acetyltransferase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic - pyruvic transaminase; GSDMD-N: gasdermin D N-terminal; H&E: hematoxylin and eosin; H3K18la: histone H3K18 lactylation; HRP: horseradish peroxidase; ICU: intensive care unit; IHC: immunohistochemistry; IL1B/IL-1B: interleukin 1 beta; IL1R1/CD121A: interleukin 1 receptor type 1; IL6/IL-6: interleukin 6; KEGG: Kyoto Encyclopedia of Genes and Genomes; LAMP1/CD107a: lysosome associated membrane protein 1; LDHA: lactate dehydrogenase A; LPS: lipopolysaccharide; 3-MA: 3-methyladenine; NLRP3/NALP3: NLR family pyrin domain containing 3; PBS: phosphate-buffered saline; PCT: procalcitonin; PMN: peripheral neutrophils; Rapa: rapamycin; RNA-seq: RNA-sequencing; SERPINE1/PAI1: serpin family E member 1; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; SOFA: Sequential Organ Failure Assessment; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TNF/TNF-alpha: tumor necrosis factor; panKla: pan-histone lactylation; VCAM1/CD106: vascular cell adhesion molecule 1. - Source: PubMed
Publication date: 2026/06/12
Li YinjiaozhiLi RanranZhu DehaoTian RuiChen YangWang XiaoliLi LeiPan TingtingTan RuomingQu Hongping - The decline of cellular proteostasis is a hallmark of aging and key contributor to neurodegenerative diseases. Protein turnover is controlled by the ubiquitin-proteasome and autophagosome-lysosome systems, but how degradation is coordinated when one of these pathways is compromised is not well understood. To study the regulation of proteostasis, we utilized human fibroblasts with targeted knockouts of the cytoskeletal factors WHAMM and JMY, which control multiple steps in autophagy. We found that cells lacking both WHAMM and JMY accumulated numerous intense foci of ubiquitinated proteins when exposed to proteotoxic stress and relied on proteasomes to clear the foci when the stressor was removed. RNA-seq and immunoblotting revealed that WHAMM/JMY knockout cells increased their expression of Synphilin-1, an α-synuclein-interacting protein implicated in Parkinson's Disease. In WHAMM/JMY knockout cells that upregulated endogenous Synphilin-1, and in cell lines engineered to overexpress mCherry-Synphilin-1, ubiquitinated proteins were present in structures containing both Synphilin-1 and proteasomes. RNAi-mediated depletion of Synphilin-1 caused a buildup of ubiquitinated proteins and the ubiquitin-binding adaptor protein SQSTM1/p62, while decreasing cell survival in response to proteotoxic stress. These data suggest that Synphilin-1 plays a pro-survival role in cells with impaired autophagy and functions in the distribution of ubiquitinated cargo during proteasomal degradation. - Source: PubMed
Publication date: 2026/06/02
Lebek Nadine MCampellone Kenneth G - Ammonia exposure can induce oxidative stress in aquatic animals. The p62 protein is a selective autophagy receptor that participates in protein degradation and oxidative stress regulation. In this study, the role of in the response of to ammonia exposure was investigated using RNA interference. The results showed that expression was significantly induced in the hepatopancreas, gills, and intestine of after ammonia exposure ( < 0.05). expression peaked at 6 h in the gills and 24 h in the intestine, whereas a biphasic response was observed in the hepatopancreas, with an initial peak at 12 h and a higher second peak at 48 h. In the RNAi experiment, knockdown altered the expression of antioxidant-related genes (, , and ) in a tissue-specific manner, with expression being prominently increased in the gills and intestine but not in the hepatopancreas under ammonia exposure. Autophagy-related genes ( and ) also showed time-dependent and tissue-specific expression changes after knockdown. The expression of apoptosis-related genes, including and , was tissue-specific and was generally lower in the dsRNA-+NH group than in the dsRNA-EGFP+NH group at most time points. Histopathological observations showed that hepatopancreatic acinar vacuolation and structural damage were alleviated, and the hepatopancreatic apoptosis rate was reduced in in the dsRNA-+NH group. These findings suggest that participates in the response of to ammonia exposure, possibly by regulating antioxidant defense, autophagy-related processes, and apoptosis, thereby affecting hepatopancreatic oxidative damage and tissue injury. - Source: PubMed
Publication date: 2026/06/04
Lu WeiLuo JunliangFeng LeyuanCai ShuanghuJian JichangYang Shiping - Circadian Locomotor Output Cycles Kaput (CLOCK) is a core circadian gene encoding a transcription factor essential for maintaining physiological rhythms, and has more recently been implicated in cancer biology. In this study, we uncover an unrecognized tumor-suppressive role of CLOCK in nasopharyngeal carcinoma (NPC). Mechanistically, CLOCK directly activates NBR1 transcription, leading to the stabilization of p62/SQSTM1 and the co-assembly of NBR1-p62 condensates via liquid-liquid phase separation (LLPS). These condensates serve as scaffolds for the recruitment of the E3 ubiquitin ligase TRIM38, which mediates the ubiquitination and proteasomal degradation of TAK1-binding protein 2 (TAB2), thereby attenuating NF-κB signaling. Functionally, this axis suppresses NPC cell proliferation and migration. Our findings reveal a novel CLOCK-NBR1/p62-TRIM38-TAB2 pathway that links circadian gene to LLPS-driven tumor suppression in NPC, providing new insights into the role of circadian genes in cancer biology and pointing to a potential therapeutic target for this malignancy. - Source: PubMed
Publication date: 2026/06/10
Rashed NasotZhu YaQuan JingLi ZhengjiangZeng PaiLi HongdeLiu WenbinZeng XiLuo Xiangjian