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 were elusive. Here we show that p14^ARF assembles into a gel-like meso-scale network upon phase separation with NPM1. This assembly

SUBMITTER: Gibbs E 

PROVIDER: S-EPMC11555371 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature