Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2

ABSTRACT: Inherited mutations in the spindle pole-associated scaffold protein WDR62 cause autosomal recessive primary microcephaly. Previous research has characterized roles of WDR62 in the regulation of spindle dynamics, cell division, and brain development. Here, we identify a new function of this protein in regulating purine metabolism. WDR62 interacts directly with BAG2, a co-chaperone of HSP70/90. Under stress conditions, WDR62 and BAG2 re-localize to cytoplasmic granules enriched for enzymes involved in purine synthesis (PFAS) and salvage (HPRT). In WDR62-deficient cells, purine synthesis is impaired, while purine deprivation leads to cytotoxicity and nucleoside accumulation. Furthermore, in these cells elevated BAG2 levels are linked to HPRT destabilization, which can be reversed by BAG2 knoc

SUBMITTER: Matthew, J. Morris 

PROVIDER: S-SCDT-10_1038-S44318-026-00724-0 | biostudies-other |

REPOSITORIES: biostudies-other