P14^ARF forms meso-scale assemblies upon phase separation with NPM1.

ABSTRACT: NPM1 is an abundant nucleolar chaperone that, in addition to facilitating ribosome biogenesis, contributes to nucleolar stress responses and tumor suppression through its regulation of the p14 Alternative Reading Frame tumor suppressor protein (p14^ARF). Oncogenic stress induces p14^ARF to inhibit MDM2, stabilize p53 and arrest the cell cycle. Under non-stress conditions, NPM1 stabilizes p14^ARF in nucleoli, preventing its degradation and blocking p53 activation. However, the mechanisms underlying the regulation of p14^ARF by NPM1 are unclear because the structural features of the p14^ARF-NPM1 complex remain elusive. Here we show that NPM1 sequesters p14^ARF within phase-separated condensates, facilitating the assembly of p14

SUBMITTER: Gibbs E 

PROVIDER: S-EPMC10723529 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature