Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Mol Sci. 2023 Jun 29;24(13):10833. doi: 10.3390/ijms241310833.
The yeast Sup35 protein misfolds into the infectious [] prion, which is then propagated by the severing activity of the molecular chaperone, Hsp104. Unlike other yeast prions, this prion is unique in that it is efficiently cured by the overexpression as well as the inactivation of Hsp104. However, it is controversial whether curing by overexpression is due to the dissolution of the prion seeds by the trimming activity of Hsp104 or the asymmetric segregation of the prion seeds between mother and daughter cells which requires cell division. To answer this question, we conducted experiments and found no difference in the extent of curing between mother and daughter cells when half of the cells were cured by Hsp104 overexpression in one generation. Furthermore, curing was not affected by the lack of Sir2 expression, which was reported to be required for asymmetric segregation of the [] seeds. More importantly, when either hydroxyurea or ethanol were used to inhibit cell division, the extent of curing by Hsp104 overexpression was not significantly reduced. Therefore, the curing of [] by Hsp104 overexpression is not due to asymmetric segregation of the prion seeds, but rather their dissolution by Hsp104.
酵母 Sup35 蛋白错误折叠成传染性[[]]朊病毒，然后由分子伴侣 Hsp104 的切割活性进行传播。与其他酵母朊病毒不同，这种朊病毒的独特之处在于，它可以通过 Hsp104 的过表达和失活有效地被治愈。然而，过表达是否能治愈的原因是 Hsp104 的修剪活性溶解了朊病毒种子，还是需要细胞分裂的朊病毒种子在母细胞和子细胞之间的不对称分离，这一点存在争议。为了回答这个问题，我们进行了实验，发现当 Hsp104 在一代中过表达以治愈一半细胞时，母细胞和子细胞之间的治愈程度没有差异。此外，治愈不受 Sir2 表达缺失的影响，据报道 Sir2 表达缺失是朊病毒种子不对称分离所必需的。更重要的是，当使用羟基脲或乙醇抑制细胞分裂时，Hsp104 过表达的治愈程度没有显著降低。因此，Hsp104 过表达对[[]]的治愈不是由于朊病毒种子的不对称分离，而是由于 Hsp104 对其的溶解。
