Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Aging Cell. 2013 Jun;12(3):518-22. doi: 10.1111/acel.12067.
Proteostasis is critical for maintaining cell function and proteome stability may play an important role in human embryonic stem cell (hESC) immortality. Notably, hESC populations exhibit a high assembly of active proteasomes, a key node of the proteostasis network. FOXO4, an insulin/IGF-1 responsive transcription factor, regulates proteasome activity in hESCs. We find that loss of FOXO4 reduces the potential of hESCs to differentiate into neural lineages. Therefore, FOXO4 crosses evolutionary boundaries and links hESC function to invertebrate longevity modulation.
蛋白质稳态对于维持细胞功能至关重要,蛋白质组的稳定性可能在人类胚胎干细胞(hESC)的永生化中发挥重要作用。值得注意的是,hESC 群体表现出高活性蛋白酶体的组装,这是蛋白质稳态网络的关键节点。FOXO4 是一种胰岛素/IGF-1 反应性转录因子,调节 hESC 中的蛋白酶体活性。我们发现,FOXO4 的缺失降低了 hESC 分化为神经谱系的潜力。因此,FOXO4 跨越了进化的界限,将 hESC 的功能与无脊椎动物的长寿调控联系起来。