Investigating the molecular basis of ARF tumor suppressor function in the nucleolus: how ARF disrupts ribosome biogenesis and function

Abstract

the ARF tumor suppressor (Alternative Reading Frame, p19Arf in mouse, p14Arf in human), is an arginine (Arg)-rich intrinsically disordered protein. During interphase, ARF is expressed at low levels and is localized to the granular component of the nucleolus through interactions with NPM1. NPM1-ARF complexes are required for the maintenance of ribosome biogenesis homeostasis. p14Arf and NPM1 associate with the nucleolar 60S preribosomal particle. ARF deletion results in a NPM1-dependent surge in ribosome biogenesis, protein synthesis and increased nucleolar size, three phenotypic hallmarks of cancer cells.