Ask about this productRelated genes to: ATG16L1 Blocking Peptide
- Gene:
- ATG16L1 NIH gene
- Name:
- autophagy related 16 like 1
- Previous symbol:
- APG16L, ATG16L
- Synonyms:
- WDR30, FLJ10035, ATG16A
- Chromosome:
- 2q37.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-22
- Date modifiied:
- 2015-11-24
Related products to: ATG16L1 Blocking Peptide
Related articles to: ATG16L1 Blocking Peptide
- Alcohol-associated liver disease (ALD) progresses from steatosis to steatohepatitis, but the underlying mechanisms remain unclear. Here, we investigated SETDB1's role in ALD progression involving LC3B-mediated LC3-associated phagocytosis (LAP). SETDB1 expression was progressively downregulated in livers of alcohol-fed mice and ethanol-treated hepatocytes, correlating with disease severity. Setdb1 HKO mice exhibited accelerated ALD progression, developing severe steatosis, inflammation, and fibrosis even under pair-fed conditions, indicating SETDB1 deficiency enhances disease susceptibility to nutritional stressors. Mechanistically, SETDB1 acted as a transcriptional cofactor for ERG to promote Map1lc3b transcription. SETDB1 deficiency impaired LAP by disrupting Rubicon membrane localization, causing defective lipid droplet clearance and enhanced cGAS-STING activation. The ATG16L1 WD40 domain was essential for this LAP-mediated protection. LC3B restoration in Setdb1 HKO mice ameliorated steatosis, inflammation, and liver injury. Notably, the lipidation-deficient LC3B-G120A mutant failed to rescue steatosis but partially suppressed inflammation, revealing a lipidation-independent LC3B function. We demonstrate lipidated LC3B mediates cytoplasmic LAP-dependent lipid clearance, while non-lipidated LC3B translocates to the nucleus, reducing R-loop accumulation, preserving genomic stability, and restraining cGAS-STING-driven inflammation. Collectively, these findings define a protective SETDB1-ERG-LC3B axis restraining ALD progression and reveal dual LC3B functions, offering mechanistic insight and a potential therapeutic strategy for intercepting steatosis-to-steatohepatitis transition. - Source: PubMed
Publication date: 2026/05/19
Zhang YiWei TanWu JiahangLin ChuixuZhu DongboLi YanhuiShi ShutingHuang ShishunJiang LeimingWang HongzhiSong MeiqiGao PengfeiWu XuFan MingjianWei ChaofengWang QianQu LihuiWang Zhigang - Mesalazine () is a first-line therapy for inflammatory bowel disease (IBD); however, its clinical use is limited by variable patient response, intolerance, and reduced efficacy in severe cases. To address these challenges, we have designed and evaluated seventeen derivatives (-) using a comprehensive in silico strategy. Density functional theory with the B3LYP/6-311++G(d,p) basis set was employed to optimize geometries and explore electronic structure, stability, and reactivity. Structural characterization was further supported by FTIR and UV-visible spectral analysis. Molecular docking against five key IBD-associated targets (TNF, NOD2, ATG16L1, IL23R, and IL6) reveled that , -, , , , , and showed stronger binding affinities than , where the and showed the strongest binding affinity. was more toxic towards the human body, although some of its derivatives were less toxic compared to , while demonstrated an overall improved ADMET profile as an IBD medication. Molecular dynamics simulations of both -NOD2 and -NOD2 complexes revealed stable behavior in each system; however, reduced structural fluctuations, flexibility, and solvent exposure, whereas promoted a more compact and conformationally restricted state, indicating distinct stabilization mechanisms, with demonstrating superior dynamic control. Collectively, these findings identify as a promising drug candidate for IBD, warranting further experimental validation through in vitro and in vivo studies. - Source: PubMed
Publication date: 2026/05/11
Rana Md SohelRabbi Md FazlayRana Enamul HaqIslam Md TanvirHossain Md SanoarMatin Shamiha BinteFarjana MuhtadiWasick Intisar HussainKumar NeerajKudrat-E-Zahan Md - The term CASM describes a process in which MAP1LC3B/LC3B and other Atg8-family proteins are covalently ligated to lipids in damaged endomembranes. While CASM is commonly described as a cytoprotective response to multiple types of membrane damage, how CASM helps cells maintain homeostasis is still unclear. Here, we show that CASM maintains Golgi apparatus architecture following the loss of TRIM46, a ubiquitin ligase with roles in microtubule organization. TRIM46 deficient cells were notable for enhanced TFEB-driven lysosomal biogenesis and Golgi ribbon fragmentation, with colocalization of the -Golgi marker TGOLN2 and the Atg8-family proteins LC3B and GABARAP. Further studies revealed that the Golgi Atg8ylation seen in knockout cells was not degradative and mechanistically resembled CASM. Genetic inhibition of CASM in TRIM46 deficient cells reduced TFEB activation and exacerbated the Golgi morphology defects, suggesting that CASM contributes to Golgi repair. Accordingly, Golgi reformation after drug-induced fragmentation was impaired upon knockdown of CASM genes. Together, these studies identify lysosomal biogenesis and CASM as coordinated features of a Golgi damage response, with CASM acting to preserve Golgi integrity. AMPK (AMP-activated protein kinase); ATG3 (autophagy related 3); ATG5 (autophagy related 5); ATG7 (autophagy related 7); ATG12 (autophagy related 12); ATG13 (autophagy related 13); ATG16L1 (autophagy related 16 like 1); BECN1 (beclin 1); CASM, conjugation of Atg8 to single membranes; GABARAP (GABA type A receptor-associated protein); GABARAPL1 (GABA type A receptor associated protein like 1); GABARAPL2 (GABA type A receptor associated protein like 2); GOLGA2 (golgin A2); HT (HaloTag); HL (HaloTag ligand); MAP1LC3A/LC3A (microtubule associated protein 1 light chain 3 alpha); MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta); MAP1LC3C/LC3C (microtubule associated protein 1 light chain 3 gamma); MTORC1 (mechanistic target of rapamycin kinase complex 1); PE (phosphatidylethanolamine); PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3); PS (phosphatidylserine); TECPR1 (tectonin beta-propellor repeat containing 1); SQSTM1/p62 (sequestosome 1); TFEB (transcription factor EB); TFE3 (transcription factor binding to IGHM enhancer 3); TGOLN2 (trans-golgi network protein 2); TRIM46 (tripartite motif containing 46); ULK1 (unc-51 like autophagy activating kinase 1); ULK2 (unc-51 like autophagy activating kinase 2): VAIL (V-ATPase-ATG16L1 induced LC3 lipidation). - Source: PubMed
Publication date: 2026/05/18
Oh SeeunUllah SaifSaha BhaskarMandell Michael A - ATG16L1 (autophagy related 16 like 1) is a core macroautophagy/autophagy protein essential for autophagosome formation. It also functions in non-canonical autophagy pathways such as LC3-associated phagocytosis (LAP) and in other processes including immunity, inflammation, and membrane trafficking. This review synthesizes recent advances and proposes that ATG16L1 functions as a central molecular integrator governed by a multi-layered regulatory code. This framework includes genetic polymorphisms, transcriptional control, and diverse post-transcriptional and post-translational mechanisms. We detail how these regulatory layers collectively fine-tune ATG16L1 function in response to cellular stress. Dysregulation of this network contributes broadly to human diseases including inflammatory bowel disease, cancer, and neurodegenerative disorders. Notably, the functional impact of specific regulatory events is highly context dependent, a principle exemplified by the Crohn disease-associated T300A polymorphism. Deciphering this regulatory landscape and its crosstalk with both autophagy-dependent and autophagy-independent functions positions ATG16L1 as a pivotal node in cellular homeostasis and as an emerging therapeutic target. ATG: autophagy related; CASM: conjugation of Atg8-family proteins to single membranes; CCD: coiled-coil domain; CEBPA/CEBPα: CCAAT enhancer binding protein alpha; CHUK/IKKA: component of inhibitor of nuclear factor kappa B kinase complex; circRNA: circular RNA; CPT1A: carnitine palmitoyltransferase 1A; CREB: cAMP responsive element binding protein; CSNK2: casein kinase 2; FTO: FTO alpha-ketoglutarate dependent dioxygenase; GJA8/connexin 50: gap junction protein alpha 8; H/R: hypoxia-reoxygenation; HDAC: histone deacetylase; KAT2B/PCAF: lysine acetyltransferase 2B; KDM1A: lysine demethylase 1A; LAP: LC3-associated phagocytosis; lncRNA: long non-coding RNA; LRRK2: leucine rich repeat kinase 2; mA: N6-methyladenosine; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; miRNA/MIR: microRNA; Mtb: ; ncRNA: non-coding RNA; PE: phosphatidylethanolamine; PI3K: phosphoinositide 3-kinase; PRKA/PKA: protein kinase cAMP-activated; PPP1: protein phosphatase 1; RAB33B: RAB33B, member RAS oncogene family; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SETD7: SET domain containing 7, histone lysine methyltransferase; SQSTM1/p62: sequestosome 1; TNF/TNF-α: tumor necrosis factor; ULK: unc-51 like autophagy activating kinase; V-ATPase: vacuolar-type H-translocating ATPase; VDR: vitamin D receptor; WIPI2B: WD repeat domain, phosphoinositide interacting 2B; YTHDF2: YTH N6-methyladenosine RNA binding protein F2; ZDHHC7: zDHHC palmitoyltransferase 7. - Source: PubMed
Publication date: 2026/05/14
Wei FujingLiu ZhenzhenYu XiaoyingSun YinqiZhao YuanyuanWang YuFeng ZilingZhao XiaozhuKe XiaoxueYang AiminCui Hongjuan - Noncanonical conjugation of ATG8 proteins, including LC3, to single membranes implicates the autophagy machinery in cell functions unrelated to metabolic stress. One such pathway is LC3-associated phagocytosis (LAP), which aids in phagosome maturation and subsequent signaling upon cargo uptake mediated by certain innate immunity-associated receptors. Here, we show that a specific isoform of RAB5 GTPases, the molecular switches controlling early endosome traffic, is necessary for LAP. We demonstrate that RAB5c regulates phagosome recruitment and function of complexes required for phosphatidylinositol 3-phosphate [PI(3)P] and reactive oxygen species (ROS) generation by macrophages. RAB5c facilitates phagosome translocation of the V-ATPase transmembrane core, which is needed for ATG16L1 binding and consequent LC3 conjugation. RAB5c depletion impaired macrophage elimination of the fungal pathogen and disruption of the V-ATPase-ATG16L1 axis increased susceptibility in vivo. Thus, early endosome-to-phagosome trafficking can be selectively engaged to promote pathogen elimination by directing phagosomal maturation toward LAP. - Source: PubMed
Publication date: 2026/05/08
Freitas-Filho Edismauro GarciaZaidan IsabellaAlzamora-Terrel Daniel LeonardoBifano CarolinaFortes-Rocha Marlonde Castro Patrícia AlvesEugênio Araujo Piraine RenanPinzan Camila Figueiredode Rezende Caroline PatiniBoada-Romero EmilioWileman ThomasAlmeida FaustoGoldman Gustavo HenriqueFlorey OliverCunha Larissa Dias