Search results for TSG101

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Protein (1 results from a total of 1)

Identifier: R-HSA-2980549
Species: Homo sapiens
Compartment: endosome membrane
Primary external reference: UniProt: TSG101: Q99816

Interactor (1 results from a total of 1)

Identifier: Q99816-1
Species: Homo sapiens
Primary external reference: UniProt: Q99816-1

Reaction (4 results from a total of 4)

Identifier: R-HSA-1169399
Species: Homo sapiens
Compartment: cytosol
Ebola virus VP40 virus-like particles (VLPs) requires the interaction of overlapping L-domains in the VP40 protein with host NEDD4 protein for efficient budding. Mono-ubiquitination of VP40 mediated by the NEDD4 E3 ligase is thought to be required for virus budding and release. ISG15 interacts with NEDD4 and inhibits the transfer of ubiquitin from the E2 enzyme to NEDD4. This prevents NEDD4-mediated ubiquitination of Ebola virus VP40 which is required for virion release.
Identifier: R-HSA-3159232
Species: Homo sapiens
Compartment: plasma membrane, cytosol, endosome membrane
The human ESCRT pathway comprises more than 30 different proteins, and this complexity is expanded further by associated regulatory and ubiquitylation machinery. Functional studies have identified a minimal core set of human ESCRT proteins, machinery that is essential for HIV-1 budding. ESCRT-1 recruitment follows an unusal path. The PTAP motif in p6 mimics the ESCRT-1 recruitment motif, bypassing the need for ESCRT-0. The TSG101/ ESCRT-I and ALIX both function by recruiting downstream ESCRT-III and VPS4 complexes, which in turn mediate membrane fission and ESCRT factor recycling.
Identifier: R-HSA-3781943
Species: Homo sapiens
Compartment: plasma membrane, endocytic vesicle membrane
Fractionation of extracellular WNT activity shows that between 12-40% of secreted WNT ligand is present on exosomal vesicles (Gross et al, 2012; Beckett et al, 2013). Exosomes are 40 - 100 nm microvesicles of endocytic origin with established roles in cell-cell communication. They are produced by multivesicular bodies (MVBs) and directed to the plasma membrane for secretion (reviewed in Simons and Raposo, 2009). WNT secretion in the exosomal fraction is dependent on WLS/EVI/SPR in both human and Drosophila cells (Gross et al, 2012; Beckett et al, 2013). While exosomes have been shown to be required for presynaptic release of EVI and Wg at Drosophila neuromuscular junctions, there is conflicting evidence about whether they play a role in the formation of a Wg gradient at the Drosophila imaginal disc (Korkut et al, 2009; Gross et al, 2012; Beckett et al, 2013). Exosomal WNT fractions co-purify with TSG101 and other components of the ESCRT machinery, and knockdown of ESCRT 0 components reduces the levels of WNT3A and the signaling activity of the exosomal fractions (Gross et al, 2012; Beckett et al, 2013).
Identifier: R-HSA-9688832
Species: Homo sapiens
Compartment: cytosol
Upon necroptosis, receptor-interacting serine/threonine protein kinase 3 (RIPK3) phosphorylates the mixed lineage kinase domain-like (MLKL) protein at Thr357 and Ser358 located in the activation loop of pseudokinase domain. The RIPK3-mediated phosphorylation relieves the inhibitory effect of the pseudokinase domain of MLKL, thus allowing the activated MLKL to oligomerize and translocate from the cytosol to cell membranes to cause membrane disintegration. Various studies showed that the endosomal sorting complexes required for transport (ESCRT) pathway can remove phosphorylated MLKL-containing membrane vesicles from cells undergoing necroptosis, thereby attenuating the cell death process (Gong YN et al. 2017; Yoon S et al. 2017; Fan W et al. 2019). The ESCRT-associated proteins, programmed cell death 6-interacting protein (PDCD6IP or ALG-2-interacting protein X, ALIX) and syntenin-1 (SDCBP), were found to mediate exocytosis of MLKL antagonizing MLKL-mediated plasma membrane alteration (Fan W et al. 2019). Protein cross-linking followed by affinity purification assays detected PDCD6IP and SDCBP in immunoprecipitates of membrane-localized MLKL isolated from human HT-29 colon cancer cells expressing a 3xFlag-HA (hemagglutinin)-tagged MLKL (Fan W et al. 2019). Knockdown of either PDCD6IP or SDCBP reduced the levels of phospho-MLKL in the exosome fractions collected from the culture medium of caspase inhibitor z-VAD-fmk-treated HT-29 cells, suggesting that phosphorylated MLKL was eventually removed from membranes through PDCD6IP:SDCBP-mediated exocytosis. Mass spectrometry and immunoblotting showed that MLKL was associated with some components of ESCRT system within extracellular vesicles (EVs) released from caspase inhibitor z-VAD-fmk-treated HT-29 cells (Yoon S et al. 2017). Further, PDCD6IP was shown to bind tumor susceptibility gene 101 (TSG101 also known as VPS23, vacuolar protein sorting 23), the ESCRT-I subunit protein (von Schwedler UK et al. 2003; Okumura M et al. 2009). Knockdown of TSG101 prevented the exocytosis of phosphorylated MLKL in HT-29 cells, further confirming that mediated exocytosis of phospho-MLKL depends on the ESCRT pathway (Fan W et al. 2019).

SDCBP (syntenin-1) interacts directly with PDCD6IP (ALIX) through three LYPX(n)L motifs located in its N-terminus and with the conserved cytoplasmic domains of the syndecans, via its PDZ domains (Baietti MF et al. 2012). Syndecans are a family of proteins that by virtue of their extracellular heparan sulfate chains interact with a plethora of signaling and adhesion molecules (Sarrazin S et al. 2011). Since PDCD6IP binds several ESCRT proteins, PDCD6IP:SDCBP adapts syndecans and syndecan cargo to the ESCRT budding machinery, playing a role in membrane budding and scission at the endosome and generating intraluminal vesicles (ILVs) that are released as exosomes when multivesicular endosomes fuse with the plasma membrane (Baietti MF et al. 2012 ). Exocytosis was proposed to counteract the effector phase of necroptosis via ESCRT-, PDCD6IP:SDCBP- or RAB27A/B-mediated expulsion of MLKL-containing bubbles to diminish the MLKL residing at the plasma membrane (Gong YN et al. 2017; Yoon S et al. 2017; Fan W et al. 2019). However, the other study suggests that membrane bubbling during necroptosis is an incredibly dynamic and heterogenous phenomenon with protrusions variously extending, retracting and shedding in a fashion seemingly independent of the primary sites of MLKL accumulation and membrane damage (Samson AL et al. 2020).

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