Other polyD/E proteins, including ANP32A and SET, can also function as stand-alone, ATP-independent molecular chaperones, disaggregases and unfoldases. These DAXX activities are ATP-independent and instead rely on the polyD/E region. DAXX can also restore native conformation and function to tumour-associated, aggregation-prone p53 mutants, reducing their oncogenic properties. Notably, DAXX effectively prevents and reverses aggregation of its in vivo-validated client proteins, the tumour suppressor p53 and its principal antagonist MDM2.
DAXX prevents aggregation, solubilizes pre-existing aggregates and unfolds misfolded species of model substrates and neurodegeneration-associated proteins. Here we show that DAXX, a polyD/E protein that has been implicated in diverse cellular processes 3-10, possesses several protein-folding activities. Moreover, proteins that contain the extensively charged poly-Asp/Glu (polyD/E) region are common in eukaryotic proteomes 2, but their biochemical activities remain undefined. At present, most known protein quality control systems are multicomponent machineries that operate via ATP-regulated interactions with non-native proteins to prevent aggregation and promote folding 1, and few systems that can broadly enable protein folding by a different mechanism have been identified. Protein quality control systems are crucial for cellular function and organismal health.