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dc.contributor.authorOhashi, Yohei
dc.date.accessioned2021-11-22T14:35:08Z
dc.date.available2021-11-22T14:35:08Z
dc.date.issued2021-11-11
dc.identifier.issn2073-4409
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330784
dc.description.abstractPhosphatidylinositol-3-phosphate (PtdIns(3)P) is essential for cell survival, and its intracellular synthesis is spatially and temporally regulated. It has major roles in two distinctive cellular pathways, namely, the autophagy and endocytic pathways. PtdIns(3)P is synthesized from phosphatidylinositol (PtdIns) by PIK3C3C/VPS34 in mammals or Vps34 in yeast. Pathway-specific VPS34/Vps34 activity is the consequence of the enzyme being incorporated into two mutually exclusive complexes: complex I for autophagy, composed of VPS34/Vps34-Vps15/Vps15-Beclin 1/Vps30-ATG14L/Atg14 (mammals/yeast), and complex II for endocytic pathways, in which ATG14L/Atg14 is replaced with UVRAG/Vps38 (mammals/yeast). Because of its involvement in autophagy, defects in which are closely associated with human diseases such as cancer and neurodegenerative diseases, developing highly selective drugs that target specific VPS34/Vps34 complexes is an essential goal in the autophagy field. Recent studies on the activation mechanisms of VPS34/Vps34 complexes have revealed that a variety of factors, including conformational changes, lipid physicochemical parameters, upstream regulators, and downstream effectors, greatly influence the activity of these complexes. This review summarizes and highlights each of these influences as well as clarifying key questions remaining in the field and outlining future perspectives.
dc.languageen
dc.publisherMDPI AG
dc.subjectVPS34
dc.subjectPtdIns(3)P
dc.subjectVPS15
dc.subjectBeclin 1
dc.subjectATG14L
dc.subjectUVRAG
dc.subjectlipids
dc.subjectmembranes
dc.subjectautophagy
dc.subjectendocytic pathway
dc.titleActivation Mechanisms of the VPS34 Complexes.
dc.typeArticle
dc.date.updated2021-11-22T14:35:07Z
prism.issueIdentifier11
prism.publicationNameCells
prism.volume10
dc.identifier.doi10.17863/CAM.78227
dcterms.dateAccepted2021-11-09
rioxxterms.versionofrecord10.3390/cells10113124
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidOhashi, Yohei [0000-0002-2288-130X]
dc.identifier.eissn2073-4409
pubs.funder-project-idMedical Research Council (MC_U105184308)
cam.issuedOnline2021-11-11


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