FAM134B Blocking Peptide
- Known as:
- FAM134B Blocking Peptide
- Catalog number:
- 33r-5466
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- FAM134B Blocking Peptide
Related genes to: FAM134B Blocking Peptide
- Gene:
- RETREG1 NIH gene
- Name:
- reticulophagy regulator 1
- Previous symbol:
- FAM134B
- Synonyms:
- FLJ20152, JK1
- Chromosome:
- 5p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 2007-05-01
- Date modifiied:
- 2019-04-23
Related products to: FAM134B Blocking Peptide
Related articles to: FAM134B Blocking Peptide
- Selective autophagy of the endoplasmic reticulum (ER), termed ERphagy or reticulophagy, plays a key role in organelle remodeling and cellular homeostasis. However, whether and how ERphagy is regulated during Gram-negative bacteria infection to influence host responses remains unclear. Here, we show that serovar Typhimurium releases lipopolysaccharide (LPS) that colocalizes with RETREG1/FAM134B, a reticulon-like ER-resident receptor for ERphagy. Cytosolic delivery of LPS, either during infection or via transfection, markedly increases RETREG1- and LC3B-decorated ER fragments. Mechanistically, affinity-isolation assays demonstrate that LPS directly binds RETREG1 through interactions between lipid A and positively charged residues within its amphipathic helices and C-terminal region. This interaction promotes RETREG1 oligomerization and drives ER membrane fragmentation, a process further amplified by the O-antigen moiety of LPS. The resulting ER fragments accumulate around LC3-positive -containing vacuoles, facilitating bacterial clearance. Importantly, both intracellular and extracellular exploit outer membrane vesicles (OMVs) to deliver LPS into the host cytosol, triggering RETREG1 activation and ER remodeling. Collectively, our findings reveal a previously unrecognized host response by which LPS of Gram-negative bacteria are sensed by the host ERphagy machinery to promote xenophagy and enhance antibacterial defense.: AH: amphipathic helix; BMDMs: bone-marrow-derived macrophages; Co-IP: co-immunoprecipitation; BafA1: bafilomycin A; Cterm: C-terminal region (Cterm); CFU: colony-forming units; DAPI: 4',6-diamidino-2-phenylindole; ER: endoplasmic reticulum; EPEC: enteropathogenic ; GBP: guanylate binding protein; Gm12250/IRGB10: predicted gene 12250; KDO: keto-3-deoxy-octonate; LPR: lipid-to-protein ratio; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; mtLIR: LC3B-interacting region mutant; MDP: muramyl dipeptide; OMVs: outer membrane vesicles; O-Ag: O-antigen; OmpA: outer membrane protein A; RHD: reticulum homology domain; R-LPS: rough-LPS; S-LPS: smooth-LPS; SCVs: -containing vacuoles; SFB: S-protein-FLAG-streptavidin binding peptide; TM: transmembrane domain; TEM: transmission electron microscopy; WT: wild-type. - Source: PubMed
Publication date: 2026/05/12
Cheng Yi-LinMello-Vieira JoãoCovarrubias-Pinto AdrianaGonzalez AlexisKumar Kuncha SantoshKew ChunZhang KaiyiAwais Afzal MuhammadDiab NourBorchert SophiaHong Siou-YingHuang Timothy ChunChen WenboMato Uxía GestalHornef Mathias WalterHübner Christian AHensel MichaelDikic Ivan - Selective autophagy of the endoplasmic reticulum (ER-phagy) is critical for ER proteostasis and host defense, yet how ER quality-control pathways interface with ER-phagy to restrict viral glycoproteins remains poorly defined. Previously, the 1 known ER-phagy receptor gene RETREG1 (RETR1)/FAM134B gene was reported to restrict Ebola virus (EBOV) replication in vivo by inhibiting the viral glycoprotein (GP) and viral protein 40 kDa (VP40) expression, but this mechanism remains unknown. Here, we identify the truncated RETR1/FAM134B isoform 2 (RETR1-2), but not its full-length protein RETR1, as an ER-phagy receptor that targets EBOV-GP for degradation. RETR1-2 broadly triggers GP degradation across ebolavirus species but not Marburg virus and inhibits EBOV replication. Mechanistically, RETR1-2 recognizes EBOV-GP via its luminal domain, undergoes GP-induced oligomerization, and directs GP-containing ER membranes to lysosomes through canonical macro-autophagy. Using unbiased mass spectrometry, we identified TOLLIP as the key cytoplasm adaptor for RETR1-2, which also requires cooperation with the ER chaperone calnexin for EBOV-GP degradation. Notably, the PI3P-binding C2 domain of TOLLIP mediates its interaction with RETR1-2, and the EBOV-GP degradation occurs independently of ubiquitination, revealing an unexpected role for TOLLIP in ER-phagy. Furthermore, EBOV-VP40 antagonizes this pathway by selectively targeting RETR1-2 for macroautophagic degradation independently of TOLLIP, thereby restoring GP expression and viral infectivity. Nevertheless, RETR1-2 reciprocally degrades VP40 via a similar mechanism. Together, these findings define a calnexin-TOLLIP-RETR1-2 axis that links ER quality control to ER-phagy-mediated antiviral restriction and uncover a reciprocal host-virus arms race centered on selective macro-autophagy. - Source: PubMed
Publication date: 2026/04/02
Zhang JingWang TaoWen JiaxinLan JingLi SunanZheng Yong-Hui - ER-phagy involves the selective autophagosomal engulfment of ER fragments, but the signaling events, selection mechanisms, and membrane source of ER-phagic autophagosomes remain elusive. Here, using state-of-the-art super-resolution multi-SIM imaging, we reveal that stresses (prolonged starvation, cholesterol dyshomeostasis, and high-Ca insults) trigger the expansion of sheet ER subdomains containing high levels of luminal Ca in mammalian cells, which are subsequently degraded by ER-phagy. Autophagosome formation and sequestration of ER sheets require the concerted actions of FAM134B and lipidated LC3, whereas the autophagy proteins ATG14 and ATG9 are partially dispensable. Electron microscopy and cryo-electron tomography show that the membranes of autophagosomes enclosing high-Ca-containing ER sheets are directly remodeled from the ER. The ER-localized cation channels PIEZO1 and TRPV1 are enriched at and mediate Ca transients from high-Ca-containing ER sheets, triggering liquid-liquid phase separation of the autophagosome-initiating FIP200 complex to initiate ER-phagy. Thus, distinct mechanisms are employed for the formation of high-Ca-containing ER-enclosing autophagosomes and non-selective autophagosomes. - Source: PubMed
Ma XiaoliCheng ZhiyangZhao HongyuZhang HuanXiao KeXie JialiFeng YunYang ChunFeng YujieWang XiXiang YaozuHu JunjieZheng QiaoxiaJi WeiZhang Hong - Dendritic cells (DCs) are crucial antigen-presenting cells that mediate the interplay between innate and adaptive immunity during lethal infections. Here, we report the key role of reticulophagy regulator 1 (RETREG1), a selective autophagy receptor, in maintaining DC maturation and function in the early stage of sepsis. Mechanistically, activating transcription factor 6 (ATF6) acts as a direct transcription factor regulating RETREG1 expression in response to bacterial lipopolysaccharide-induced endoplasmic reticulum (ER) stress. RETREG1-mediated reticulophagy reduces excessive ER stress via the eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) signaling pathway and inhibits membrane-associated RING-CH-type finger 8 (MARCH8)-dependent major histocompatibility complex class II (MHC-II) ubiquitination to maintain antigen presentation in DCs. Consequently, Cd11cRetreg1, Retreg1, and Atf6 mice exhibit impaired DC function, leading to immunosuppression and multiple organ failure in experimental sepsis. Exploration of samples from septic patients, combined with single-cell bioinformatics analysis, further suggests that a deficit in reticulophagy in DCs is associated with the development of human sepsis. - Source: PubMed
Publication date: 2026/03/24
Yao Ren-QiRen ChaoZheng Li-YuLi Jing-YanWu Wen-FengLi Yu-XuanWang Li-XueDuan YuWang LuLiu Shuang-QingHe Peng-YiZhao Peng-YueTong SenLi Zhi-XuanZhang TuoWu Meng-YaoWei Shu-TingDong NingWu YaoZhang HuiZhu Xiao-MeiZhang Zi-ChengWu Guo-ShengXia Zhao-FanDu Xiao-HuiKang Hong-JunZou ZuiTang Dao-LinYao Yong-Ming - Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase of the TRIM superfamily, modulates critical cellular processes including ubiquitination, autophagy, and oxidative stress response. Accumulating evidence highlights its context-dependent regulatory roles in hepatocellular carcinoma (HCC)-the most prevalent primary liver malignancy with high mortality and limited therapeutic efficacy. This review systematically summarizes the core mechanisms by which TRIM21 orchestrates HCC progression: ① Autophagy regulation: TRIM21 modulates HCC autophagy via multiple axes, including CCR4-NOT complex (TNKS1BP1/CNOT4)-mediated substrate ubiquitination, ATG14-dependent autophagosome initiation, and RETREG1-driven reticulophagy, with context-dependent effects on tumor proliferation. ② Drug resistance: TRIM21 enhances oxaliplatin sensitivity by ubiquitinating and degrading G6PD (the rate-limiting enzyme of the pentose phosphate pathway), while its role in sorafenib resistance involves dual pathways-the MST1/YAP axis and the ApoE/cholesterol/PI3K-AKT cascade. ③ Metastasis suppression: TRIM21 restricts HCC invasion and metastasis by ubiquitinating key oncoproteins, preserving epithelial integrity and inhibiting mesenchymal transition. ④ Reactive oxygen species (ROS) balance: TRIM21 regulates oxidative stress in HCC via the SQSTM1/p62-Keap1-NRF2 axis, coordinating with HIF1α to modulate antioxidant responses and tumor cell survival. Additionally, we discuss the regulatory significance of TRIM21 in HCC associated with hepatitis B virus (HBV) infection (via HBx/DNA polymerase ubiquitination) and nonalcoholic steatohepatitis (NASH) (via suppressing lipogenic enzymes to reduce steatosis-driven carcinogenesis). This review provides a theoretical basis for TRIM21 as a potential diagnostic marker and therapeutic target for HCC. - Source: PubMed
Publication date: 2026/01/13
Sun JiatongGao ZixuanLi YuanhaoGao JiajunWang PeiyinQin YiboChen YanruZhang Ruihong