TSG101

TSG101 (tumor susceptibility gene 101 / ESCRT-I)

一行要約

ESCRT (Endosomal Sorting Complex Required for Transport) 機構の ESCRT-I サブコンプレックスのコアサブユニット。N 末端の UEV (ubiquitin E2 variant) ドメインで MVB cargo の K63 ubiquitin chain と HRS (ESCRT-0) の PSAP motif を認識し、ESCRT-II / ESCRT-III をリクルートして intraluminal vesicle (ILV) 形成 (inward budding と scission) を駆動する。エクソソーム biogenesis の canonical (ESCRT-依存) 経路の rate-limiting factor であり、HIV-1 など多くのエンベロープウイルスの budding でも宿主側因子として hijack される。

主要エビデンス

MVB / ILV 形成: TSG101 KD は cargo (EGFR-Ub, MHC class II 等) の MVB inward budding を阻害し、ILV 形成と引き続くエクソソーム放出を顕著に減少させる。

腫瘍生物学: TSG101 は当初 tumor suppressor 候補として同定されたが、その後 ESCRT 主要因子としての機能が中心と認識された。腫瘍由来エクソソーム分泌量は TSG101 発現量と概ね相関する。

ウイルス budding: HIV-1 Gag p6 領域の PTAP motif が TSG101 UEV と結合し、ESCRT-III を hijack して virion budding を完了させる。HTLV-1, ebola など多くのエンベロープウイルスで保存。

メカニズム

ESCRT-I 複合体: TSG101 (VPS23) + VPS28 + VPS37A-D + MVB12A/B のヘテロ 5 量体。TSG101 UEV ドメインが Ub-cargo / PTAP motif を認識し、C 末端 steadiness ドメインで VPS28 と結合。

ILV 形成カスケード:

1. ESCRT-0 (HRS-STAM) が ubiquitinated cargo を MVB 限界膜に clustering
2. ESCRT-I (TSG101 含む) が cargo を受け取り
3. ESCRT-II (EAP30/45/20) を介して
4. ESCRT-III (CHMP4 等) が membrane scission を実行
5. VPS4 ATPase が ESCRT-III を recycle

ALIX 経路との関係: ESCRT-I 経由とは独立に、ALIX が ESCRT-III を直接リクルートする副経路 (syndecan-syntenin-ALIX route) も存在し、TSG101 と ALIX は機能的に補完的。

関連エンティティ・概念

• ESCRT machinery: ALIX — ESCRT-associated accessory protein
• Syndecan-syntenin-ALIX route: Syntenin
• Tetraspanin EV markers: CD9 / CD63 / CD81
• Trafficking: Rab27
• Pathway: Exosome-biogenesis-pathway
• Concept: EV-mediated-intercellular-communication / EV-organotropism / Exosomal-PD-L1
• MOC: cancer-extracellular-vesicles

関連論文

直近 30 件のみ表示中 (関連 155 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Extracellular vesicles

• Liu et al. ACSApplMaterInterfaces 2024 — Cell-specific impacts of surface coating composition on extracellular vesicle secretion
• Clancy et al. AnnuRevPathol 2023 — Tumor-derived extracellular vesicles multifunctional entities in the tumor microenvironment
• Tang et al. BrainRes 2023 — Activated neutrophil-derived exosomes contribute to blood-brain barrier damage and hemorrhagic transformation after
• Patras et al. CancerCell 2023 — Immune determinants of the pre-metastatic niche
• Casanova-Salas et al. CancerCell 2024 — Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution
• Xue et al. CancerCellInt 2026 — Tissue-derived extracellular vesicles comparing ts-EVs and te-EVs in extraction, characteristics and research trends
• Tsering et al. CellDeathDis 2024 — Extracellular vesicle-associated DNA ten years since its discovery in human blood
• Wang et al. CellMetab 2023 — Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment
• Peng et al. CellMolBiolLett 2026 — Lactate-activated astrocytes promote NSCLC brain metastasis through extracellular vesicle-mediated miR-8085trim67elk1
• Chen et al. FrontImmunol 2026 — Exosomal POSTN from cancer-associated fibroblasts drives progression of microinvasive lung adenocarcinoma insights from
• Xie et al. IntImmunopharmacol 2025 — Neutrophil-derived exosomes promote sepsis-related multiple organ dysfunction through the induction of neutrophil
• Yang et al. JClinInvest 2025 — HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin beta3-containing
• Pontis et al. JExpClinCancerRes 2026 — Circulating extracellular vesicles from early-stage lung cancer patients trigger endothelial activation to drive
• Mugoni et al. JExtracellBiol 2023 — Integrating extracellular vesicle and circulating cell-free DNA analysis using a single plasma aliquot improves the
• Crescitelli et al. JExtracellVesicles 2025 — Recommendations for studying in situ extracellular vesicles from solid tissue
• Li et al. JExtracellVesicles 2026 — Exosomal oleic acid promotes lymphangiogenesis and nodal metastasis in cervical cancer via the AKTmTOR pathway
• Xie et al. JExtracellVesicles 2026 — Predictor a non-enzymatic catalytic cascade tool for in situ visualization of small extracellular vesicle surface
• Liu et al. JNanobiotechnology 2026 — Overcoming blood-brain barrier and chemoresistance in glioblastoma by angiopep-2-modified NK cell-derived extracellular
• Cai et al. MolCancer 2026 — Extracellular vesicles in solid tumors from tumor ecology to engineered therapeutics
• Radler et al. MolTher 2023 — Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading
• Tian et al. NatBiomedEng 2026 — Skeletal-muscle-targeted non-viral delivery of full-length DMD mRNA for duchenne muscular dystrophy
• Wen et al. NatBiotechnol 2026 — Spatially resolved profiling of extracellular vesicles in tissues with spatial-EV-seq
• Yu et al. NatCommun 2025 — Defective neutrophil-derived exosomes facilitate macrophage activation through miR-122-5p in Behcet’s disease
• Shen et al. NatCommun 2026 — Co-enrichment of proteins in extracellular vesicles
• Dixson et al. NatRevMolCellBiol 2023 — Context-specific regulation of extracellular vesicle biogenesis and cargo selection
• Guo et al. SciAdv 2026 — Helper lipid-engineered extracellular vesicles enable PET imaging-guided pulmonary siRNA delivery to treat lung
• Jeppesen et al. TrendsCellBiol 2023 — Extracellular vesicles and nanoparticles emerging complexities

Basic-Immunotherapy

• Ikeda et al. Nature 2025 — Immune evasion through mitochondrial transfer in the tumour microenvironment

Basic-Neutrophil and myeloid cell

• Hsu et al. Cell 2025 — Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution
• Li et al. MolImmunol 2025 — Neutrophil-derived exosomal S100A8 aggravates lung injury in sepsis by inducing pyroptosis