论文
论文标题：DAXX represents a new type of protein-folding enabler
作者：Huang, Liangqian, Agrawal, Trisha, Zhu, Guixin, Yu, Sixiang, Tao, Liming, Lin, JiaBei, Marmorstein, Ronen, Shorter, James, Yang, Xiaolu
期刊：Nature
发表时间：2021/08/18
数字识别码：10.1038/s41586-021-03824-5
摘要：Protein quality control systems are crucial for cellular function and organismal health. 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 folding1, and few systems that can broadly enable protein folding by a different mechanism have been identified. Moreover, proteins that contain the extensively charged poly-Asp/Glu (polyD/E) region are common in eukaryotic proteomes2, but their biochemical activities remain undefined. Here we show that DAXX, a polyD/E protein that has been implicated in diverse cellular processes3,4,5,6,7,8,9,10, possesses several protein-folding activities. DAXX prevents aggregation, solubilizes pre-existing aggregates and unfolds misfolded species of model substrates and neurodegeneration-associated proteins. Notably, DAXX effectively prevents and reverses aggregation of its in vivo-validated client proteins, the tumour suppressor p53 and its principal antagonist MDM2. DAXX can also restore native conformation and function to tumour-associated, aggregation-prone p53 mutants, reducing their oncogenic properties. These DAXX activities are ATP-independent and instead rely on the polyD/E region. Other polyD/E proteins, including ANP32A and SET, can also function as stand-alone, ATP-independent molecular chaperones, disaggregases and unfoldases. Thus, polyD/E proteins probably constitute a multifunctional protein quality control system that operates via a distinctive mechanism.
参考资料：
[1] Huang, L., et al. (2021) DAXX represents a new type of protein-folding enabler. Nature. doi.org/10.1038/s41586-021-03824-5.
[2] Restoring “Chaperone” Protein May Prevent Plaque Build-up in Alzheimer’s. Retrieved Sep. 2, 2021 from https://www.pennmedicine.org/new ... ld-up-in-alzheimers
