Spatial alterations of De Novo purine biosynthetic enzymes by Akt-independent PDK1 signaling pathways

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dc.contributor.authorSchmitt, Danielle L.
dc.contributor.authorSundaram, Anand
dc.contributor.authorJeon, Miji
dc.contributor.authorLuu, Bao Tran
dc.contributor.authorAn, Songon
dc.date.accessioned2018-05-17T18:18:21Z
dc.date.available2018-05-17T18:18:21Z
dc.date.issued2018
dc.description.abstractA macromolecular complex of the enzymes involved in human de novo purine biosynthesis, the purinosome, has been shown to consist of a core assembly to regulate the metabolic activity of the pathway. However, it remains elusive whether the core assembly itself can be selectively controlled in the cytoplasm without promoting the purinosome. Here, we reveal that pharmacological inhibition of the cytoplasmic activity of 3-phosphoinositide-dependent protein kinase 1 (PDK1) selectively promotes the formation of the core assembly, but not the purinosome, in cancer cells. However, alternative signaling cascades that are associ-ated with the plasma membrane-bound PDK1 activity, including Akt-mediated cascades, regulate neither the core assembly nor the purinosome in our conditions. Along with immu-nofluorescence microscopy and a knock-down study against PDK1 using small interfering RNAs, we reveal that cytoplasmic PDK1-associated signaling pathways regulate subcellular colocalization of three enzymes that form the core assembly of the purinosome in an Akt-independent manner. Collectively, this study reveals a new mode of compartmentalization of purine biosynthetic enzymes controlled by spatially resolved signaling pathways.en_US
dc.format.extent15 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/M2SN0171C
dc.identifier.citationArticle Source: Spatial alterations of De Novo purine biosynthetic enzymes by Akt-independent PDK1 signaling pathways Schmitt DL, Sundaram A, Jeon M, Luu BT, An S (2018) Spatial alterations of De Novo purine biosynthetic enzymes by Akt-independent PDK1 signaling pathways. PLOS ONE 13(4): e0195989. https://doi.org/10.1371/journal.pone.0195989en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0195989
dc.identifier.urihttp://hdl.handle.net/11603/10773
dc.language.isoen_USen_US
dc.publisherPLOS ONEen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemistry & Biochemistry Department Collection
dc.relation.ispartofUMBC Student Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsAttribution 4.0 International (CC BY 4.0)*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjecthuman purine biosynthesisen_US
dc.subjectpurinosomeen_US
dc.subjectsignaling pathwaysen_US
dc.subjectenzymesen_US
dc.titleSpatial alterations of De Novo purine biosynthetic enzymes by Akt-independent PDK1 signaling pathwaysen_US
dc.typeTexten_US

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