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

ABSTRACT: A 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 associated with the plasma membrane-bound PDK1 activity, including Akt-mediated cascades, regulate neither the core assembly nor the purinosome in our conditions. Along with immuno

SUBMITTER: Schmitt DL 

PROVIDER: S-EPMC5905998 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature