endosomal sorting complexes required for transport


Summary: A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.

Top Publications

  1. Tsuchiya H, Ohtake F, Arai N, Kaiho A, Yasuda S, Tanaka K, et al. In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome. Mol Cell. 2017;66:488-502.e7 pubmed publisher
    ..Collectively, our results provide an overall picture of the ubiquitin network via UBD proteins and identify the Cdc48-Rad23/Dsk2 axis as a major route to the proteasome. ..
  2. Horn A, Celic I, Dong C, Martirosyan I, Han J. A conserved role for the ESCRT membrane budding complex in LINE retrotransposition. PLoS Genet. 2017;13:e1006837 pubmed publisher
    ..This study highlights the importance of the ESCRT complex in the L1 life cycle and suggests an unusual mode for L1 RNP trafficking. ..
  3. Burke B. CELL BIOLOGY. When cells push the envelope. Science. 2016;352:295-6 pubmed publisher
  4. Su J, Zhou X, Yin X, Wang L, Zhao Z, Hou Y, et al. The effects of curcumin on proliferation, apoptosis, invasion, and NEDD4 expression in pancreatic cancer. Biochem Pharmacol. 2017;140:28-40 pubmed publisher
    ..These results suggested that inhibition of NEDD4 might be beneficial to the antitumor properties of curcumin on PC treatments. ..
  5. Xia H, Shao D, Liu X, Wang Q, Zhou Y, Chen K. Identification and Characterization of BmVta1, a Bombyx mori (Lepidoptera: Bombycidae) Homologue for Vta1 That is Up-Regulated in Development. J Insect Sci. 2017;17: pubmed publisher
  6. McMillan K, Korswagen H, Cullen P. The emerging role of retromer in neuroprotection. Curr Opin Cell Biol. 2017;47:72-82 pubmed publisher
  7. Vandenabeele P, Riquet F, Cappe B. Necroptosis: (Last) Message in a Bubble. Immunity. 2017;47:1-3 pubmed publisher
    ..Two independent reports-in Immunity (Yoon et al., 2017) and Cell (Gong et al., 2017)-reveal that MLKL affects homeostatic membrane trafficking and necroptosis-enhanced bubble formation involving interaction with the ESCRT machinery. ..
  8. González A, Muñoz V, Cavieres V, Bustamante H, Cornejo V, Januário Y, et al. Autophagosomes cooperate in the degradation of intracellular C-terminal fragments of the amyloid precursor protein via the MVB/lysosomal pathway. FASEB J. 2017;31:2446-2459 pubmed publisher
    ..daSilva, L. L., Rojas-Fernández, A., Hay, R. T., Mardones, G. A., Burgos, P. V. Autophagosomes cooperate in the degradation of intracellular C-terminal fragments of the amyloid precursor protein via the MVB/lysosomal pathway. ..
  9. White J, Toptygin D, Cohen R, Murphy N, Hilser V. Structural Stability of the Coiled-Coil Domain of Tumor Susceptibility Gene (TSG)-101. Biochemistry. 2017;56:4646-4655 pubmed publisher
    ..These results support a model whereby the tetramer-monomer equilibrium of TSG101 serves as the cellular reservoir of TSG101, which is effectively outcompeted when its binding partners are present and the heteroternary complex can form...

More Information


  1. Xu B, Fu Y, Liu Y, Agvanian S, Wirka R, Baum R, et al. The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles. PLoS Biol. 2017;15:e2002354 pubmed publisher
    ..Exploring putative mechanisms of MP release, we found that the membrane fission complex endosomal sorting complexes required for transport (ESCRT)-III subunit charged multivesicular body protein 4B (CHMP4B) colocalizes and ..
  2. Panwalkar V, Neudecker P, Willbold D, Dingley A. Multiple WW domains of Nedd4-1 undergo conformational exchange that is quenched upon peptide binding. FEBS Lett. 2017;591:1573-1583 pubmed publisher
    ..Thus, the binding mechanism of hNedd4-1 WW domains to proteins involves coupled folding and binding equilibria, and this mechanism may be a general feature that modulates peptide affinities of WW domains. ..
  3. Qiu Y, Zheng Y, Wu K, Schulman B. Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4. Protein Sci. 2017;26:1674-1680 pubmed publisher
    ..The data provide detailed molecular insights underlying recruitment of an E3 ubiquitin ligase to phagophores during autophagy. ..
  4. Weng M, Luo Z, Wu X, Zeng W. The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates pancreatic cancer. Oncotarget. 2017;8:20288-20296 pubmed publisher
    ..Therefore, NEDD4 may be a potential therapeutic target in PDAC. ..
  5. Mierzwa B, Chiaruttini N, Redondo Morata L, von Filseck J, König J, Larios J, et al. Dynamic subunit turnover in ESCRT-III assemblies is regulated by Vps4 to mediate membrane remodelling during cytokinesis. Nat Cell Biol. 2017;19:787-798 pubmed publisher
    ..Continuous ESCRT-III remodelling by subunit turnover might facilitate shape adaptions to variable membrane geometries, with broad implications for diverse cellular processes. ..
  6. Luo Z, Ge M, Chen J, Geng Q, Tian M, Qiao Z, et al. HRS plays an important role for TLR7 signaling to orchestrate inflammation and innate immunity upon EV71 infection. PLoS Pathog. 2017;13:e1006585 pubmed publisher
  7. Henne W, Stenmark H, Emr S. Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Biol. 2013;5: pubmed publisher
    The endosomal sorting complexes required for transport (ESCRT) drive multivesicular body (MVB) biogenesis and cytokinetic abscission...
  8. Leslie N, Spinelli L, Tibarewal P, Zilidis G, Weerasinghe N, Lim J, et al. Indirect mechanisms of carcinogenesis via downregulation of PTEN function. Adv Enzyme Regul. 2010;50:112-8 pubmed publisher
  9. Skowyra M, Schlesinger P, Naismith T, Hanson P. Triggered recruitment of ESCRT machinery promotes endolysosomal repair. Science. 2018;360: pubmed publisher
    ..Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts. ..
  10. Liu Z, Huo X, Zhao S, Yang J, Shi W, Jing L, et al. Low density lipoprotein receptor class A domain containing 4 (LDLRAD4) promotes tumorigenesis of hepatic cancer cells. Exp Cell Res. 2017;360:189-198 pubmed publisher
    ..In addition, depletion of LDLRAD4 in HepG2 liver cancer cells inhibited tumorigenesis in nude mice. These results reveal an oncogenic role of LDLRAD4 in tumorigenesis through its association with Nedd4. ..
  11. Trimpert C, Wesche D, de Groot T, Pimentel Rodriguez M, Wong V, van den Berg D, et al. NDFIP allows NEDD4/NEDD4L-induced AQP2 ubiquitination and degradation. PLoS ONE. 2017;12:e0183774 pubmed publisher
    ..As NDFIP1/2 bind many NEDD4 family E3 ligases, which are implicated in several cellular processes, NDFIP1/2 may be the missing link for AQP2 ubiquitination and degradation from different subcellular locations. ..
  12. Ribich S, Harvey D, Copeland R. Drug Discovery and Chemical Biology of Cancer Epigenetics. Cell Chem Biol. 2017;24:1120-1147 pubmed publisher
    ..Additionally, we highlight the CMPs for which potent inhibitors have not been developed and additional research focus should be dedicated. ..
  13. Xu H, Miao Z, Wang Z, Zhao T, Xu Y, Song Y, et al. HCRP1 downregulation confers poor prognosis and induces chemoresistance through regulation of EGFR-AKT pathway in human gastric cancer. Virchows Arch. 2017;471:743-751 pubmed publisher
    ..In conclusion, our results suggest that HCRP1 downregulation might serve as an indicator for poor prognosis in gastric cancer patients. HCRP1 reduces drug resistance through regulation of EGFR-AKT signaling. ..
  14. Kasahara K, Aoki H, Kiyono T, Wang S, Kagiwada H, Yuge M, et al. EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase. Nat Commun. 2018;9:758 pubmed publisher
    ..We further show that usp8 knockout zebrafish develops ciliopathy-related phenotypes including cystic kidney, suggesting that USP8 is a regulator of ciliogenesis in vertebrates. ..
  15. Kuo L, Freed E. ARRDC1 as a mediator of microvesicle budding. Proc Natl Acad Sci U S A. 2012;109:4025-6 pubmed publisher
  16. Temkin P, Morishita W, Goswami D, Arendt K, Chen L, Malenka R. The Retromer Supports AMPA Receptor Trafficking During LTP. Neuron. 2017;94:74-82.e5 pubmed publisher
    ..These findings demonstrate a key role for the retromer in LTP and provide insights into how retromer malfunction in the mature brain may contribute to symptoms of common neurodegenerative diseases. VIDEO ABSTRACT. ..
  17. Holm I, Isaacs A, Mackenzie I. Absence of FUS-immunoreactive pathology in frontotemporal dementia linked to chromosome 3 (FTD-3) caused by mutation in the CHMP2B gene. Acta Neuropathol. 2009;118:719-20 pubmed publisher
  18. Park M, Upton D, Blackmon M, Dixon V, Craver S, Neal D, et al. Anacardic acid inhibits pancreatic cancer cell growth, and potentiates chemotherapeutic effect by Chmp1A - ATM - p53 signaling pathway. BMC Complement Altern Med. 2018;18:71 pubmed publisher
    ..Our data suggests that Anacardic Acid might be a promising complementary supplement to slow the initiation or progression of pancreatic cancer. ..
  19. Sundquist W, Ullman K. CELL BIOLOGY. An ESCRT to seal the envelope. Science. 2015;348:1314-5 pubmed publisher
  20. Bachofner M, Speicher T, Bogorad R, Muzumdar S, Derrer C, Hürlimann F, et al. Large-Scale Quantitative Proteomics Identifies the Ubiquitin Ligase Nedd4-1 as an Essential Regulator of Liver Regeneration. Dev Cell. 2017;42:616-625.e8 pubmed publisher
    ..Finally, they identify an essential function of Nedd4-1 in tissue repair. ..
  21. Haag C, Pohlmann T, Feldbrügge M. The ESCRT regulator Did2 maintains the balance between long-distance endosomal transport and endocytic trafficking. PLoS Genet. 2017;13:e1006734 pubmed publisher
    ..In conclusion, the ESCRT regulator Did2 coordinates precise maturation of endosomes and thus provides the correct membrane identity for efficient endosomal long-distance transport. ..
  22. Franquelim H, Schwille P. Revolving around constriction by ESCRT-III. Nat Cell Biol. 2017;19:754-756 pubmed publisher
    ..A study of the dynamic assembly and disassembly of the ESCRT-III machinery in vitro and in vivo now suggests that the turnover of the observed spiralling filaments is critical for membrane abscission during cytokinesis. ..
  23. Sun H, Ma H, Wang J, Xia L, Zhu G, Wang Z, et al. Phosphatase and tensin homolog deleted on chromosome 10 degradation induced by NEDD4 promotes acquired erlotinib resistance in non-small-cell lung cancer. Tumour Biol. 2017;39:1010428317709639 pubmed publisher
    ..Targeted decrease in NEDD4 expression may be a potential therapeutic strategy for tyrosine kinase inhibitor-resistant non-small-cell lung cancer. ..
  24. Lippincott Schwartz J, Freed E, van Engelenburg S. A Consensus View of ESCRT-Mediated Human Immunodeficiency Virus Type 1 Abscission. Annu Rev Virol. 2017;4:309-325 pubmed publisher
    ..To provide a template for further refinement, we propose a new working model for ESCRT-mediated HIV-1 release that reconciles disparate and seemingly conflicting studies. ..
  25. Gong Y, Guy C, Olauson H, Becker J, Yang M, Fitzgerald P, et al. ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences. Cell. 2017;169:286-300.e16 pubmed publisher
    ..As a consequence of the action of ESCRT-III, cells undergoing necroptosis can express chemokines and other regulatory molecules and promote antigenic cross-priming of CD8+ T cells. ..
  26. Zhao G, Zhang P, Gong J, Zhang X, Wang P, Yin M, et al. Tmbim1 is a multivesicular body regulator that protects against non-alcoholic fatty liver disease in mice and monkeys by targeting the lysosomal degradation of Tlr4. Nat Med. 2017;23:742-752 pubmed publisher
    ..Taken together, these findings could lead to the development of promising strategies to treat NASH by targeting MVB regulators to properly orchestrate the lysosome-mediated protein degradation of key mediators of the disease. ..
  27. Alvaro C, O Donnell A, Prosser D, Augustine A, Goldman A, Brodsky J, et al. Specific ?-arrestins negatively regulate Saccharomyces cerevisiae pheromone response by down-modulating the G-protein-coupled receptor Ste2. Mol Cell Biol. 2014;34:2660-81 pubmed
    ..Finally, we show that Rod1 function requires calcineurin-dependent dephosphorylation. ..
  28. Huang C, Shi Y, Zhao Y. USP8 mutation in Cushing's disease. Oncotarget. 2015;6:18240-1 pubmed
  29. Park H, Ryu D, Parmar M, Giasson B, McFarland N. The ER retention protein RER1 promotes alpha-synuclein degradation via the proteasome. PLoS ONE. 2017;12:e0184262 pubmed publisher
    ..Further investigation of the mechanism of RER1 and downstream effectors on ?Syn may yield novel therapeutic targets for modulation in Parkinson disease and related synucleinopathies. ..
  30. Zhang Y, He X, Meng X, Wu X, Tong H, Zhang X, et al. Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model. Cell Death Dis. 2017;8:e2574 pubmed publisher
    ..Furthermore, the SGK/PKC pathway is regulated downstream of Nedd4-2 in MPTP-treated mice. These findings indicate that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. ..
  31. Buono R, Leier A, Paez Valencia J, Pennington J, Goodman K, Miller N, et al. ESCRT-mediated vesicle concatenation in plant endosomes. J Cell Biol. 2017;216:2167-2177 pubmed publisher
    ..Consistent with a potential role as a diffusion barrier, we find that the ESCRT-III protein SNF7 remains associated with ILVs and is delivered to the vacuole for degradation. ..
  32. Chen Z, Jiang H, Xu W, Li X, Dempsey D, Zhang X, et al. A Tunable Brake for HECT Ubiquitin Ligases. Mol Cell. 2017;66:345-357.e6 pubmed publisher
    ..These results clarify the mechanisms of several HECT protein cancer associated mutations and provide a new framework for understanding how HECT ubiquitin ligases must be finely tuned to ensure normal cellular behavior. ..
  33. Kovalev N, Inaba J, Li Z, Nagy P. The role of co-opted ESCRT proteins and lipid factors in protection of tombusviral double-stranded RNA replication intermediate against reconstituted RNAi in yeast. PLoS Pathog. 2017;13:e1006520 pubmed publisher
    ..We show that deletion of the co-opted ESCRT-I (endosomal sorting complexes required for transport I) or ESCRT-III factors makes TBSV replication more sensitive to the RNAi machinery in yeast...
  34. Roche J, Survery S, Kreida S, Nesverova V, Ampah Korsah H, Gourdon M, et al. Phosphorylation of human aquaporin 2 (AQP2) allosterically controls its interaction with the lysosomal trafficking protein LIP5. J Biol Chem. 2017;292:14636-14648 pubmed publisher
  35. Worst T, Meyer Y, Gottschalt M, Weis C, von Hardenberg J, Frank C, et al. RAB27A, RAB27B and VPS36 are downregulated in advanced prostate cancer and show functional relevance in prostate cancer cells. Int J Oncol. 2017;50:920-932 pubmed publisher
    ..The ESCRT machinery (endosomal sorting complexes required for transport) and Rab-proteins act as key players in vesicular trafficking and secretion...
  36. Oku M, Maeda Y, Kagohashi Y, Kondo T, Yamada M, Fujimoto T, et al. Evidence for ESCRT- and clathrin-dependent microautophagy. J Cell Biol. 2017;216:3263-3274 pubmed publisher
    ..This study sheds light on the molecular mechanism of microautophagy, which does not require the core Atg proteins. ..
  37. Scourfield E, Martin Serrano J. Growing functions of the ESCRT machinery in cell biology and viral replication. Biochem Soc Trans. 2017;45:613-634 pubmed publisher
    ..These advances are discussed in the context of areas of cell biology that have been transformed by research in the ESCRT field, including cytokinetic abscission, nuclear envelope resealing and plasma membrane repair. ..
  38. Adoro S, Park K, Bettigole S, Lis R, Shin H, Seo H, et al. Post-translational control of T cell development by the ESCRT protein CHMP5. Nat Immunol. 2017;18:780-790 pubmed publisher
    ..Our results thus identify CHMP5 as an essential component of the post-translational machinery required for T cell development. ..
  39. Zaglia T, Milan G, Ruhs A, Franzoso M, Bertaggia E, Pianca N, et al. Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy. J Clin Invest. 2014;124:2410-24 pubmed publisher
    ..These data indicate that atrogin-1 promotes cardiomyocyte health through mediating the interplay between UPS and autophagy/lysosome system and its alteration promotes development of cardiomyopathies. ..
  40. Guzzo C, Matunis M. Expanding SUMO and ubiquitin-mediated signaling through hybrid SUMO-ubiquitin chains and their receptors. Cell Cycle. 2013;12:1015-7 pubmed publisher
  41. Niu Z, Pang R, Liu W, Li Q, Cheng R, Yeung W. Polymer-based precipitation preserves biological activities of extracellular vesicles from an endometrial cell line. PLoS ONE. 2017;12:e0186534 pubmed publisher
    ..The simple setup and low equipment demands makes PBP the most suitable method for rapid EV assessment and isolation of EVs in clinical and basic research settings...
  42. Barclay R, Schwab A, DeMarino C, Akpamagbo Y, Lepene B, Kassaye S, et al. Exosomes from uninfected cells activate transcription of latent HIV-1. J Biol Chem. 2017;292:11682-11701 pubmed publisher
  43. Shrestha P, Yun J, Ko Y, Yeon K, Kim D, Lee H, et al. NMR uncovers direct interaction between human NEDD4-1 and p34SEI-1. Biochem Biophys Res Commun. 2017;490:984-990 pubmed publisher
    ..Our data will provide insights into the molecular mechanism of NEDD4-1 and p34SEI-1 interaction, which will be directly used for drug design which inhibits the molecular interaction involved in different cancer signaling. ..
  44. Zhu B, Das S, Mitra S, Farris T, McBride J. Ehrlichia chaffeensis TRP120 Moonlights as a HECT E3 Ligase Involved in Self- and Host Ubiquitination To Influence Protein Interactions and Stability for Intracellular Survival. Infect Immun. 2017;85: pubmed publisher
    ..chaffeensis ubiquitin ligase and revealed an important role for the ubiquitin pathway in effector-host interactions and pathogen-mediated host protein stability in order to promote intracellular survival. ..
  45. Shirata N, Ihara K, Yamamoto Nonaka K, Seki T, Makino S, Oliva Trejo J, et al. Glomerulosclerosis Induced by Deficiency of Membrane-Associated Guanylate Kinase Inverted 2 in Kidney Podocytes. J Am Soc Nephrol. 2017;28:2654-2669 pubmed publisher
    ..In summary, MAGI-2 and Fyn protect dendrin from Nedd4-2-mediated ubiquitination and from nuclear translocation, thereby maintaining the physiologic homeostasis of podocytes, and the lack of MAGI-2 in podocytes results in FSGS. ..
  46. Faucz F, Tirosh A, Tatsi C, Berthon A, Hernández Ramírez L, Settas N, et al. Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease. J Clin Endocrinol Metab. 2017;102:2836-2843 pubmed publisher
    ..Patients harboring a somatic mutation had a higher likelihood of tumor recurrence, highlighting the potential importance of this molecular defect for the disease prognosis and the development of targeted therapeutic options. ..