The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
J Biol Chem. 2011 Mar 4;286(9):6946-54. doi: 10.1074/jbc.M110.172338. Epub 2010 Dec 23.
The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability. Finally, RSK2 blocks Fas-induced apoptosis through its phosphorylation of caspase-8. These data provide a direct link between RSK2 and caspase-8 and identify a novel molecular mechanism for caspase-8 modulation by RSK2.
核糖体 S6 激酶 2（RSK2）是 p90 核糖体 S6 激酶（p90RSK）家族蛋白的成员，在增殖、细胞周期和细胞转化中发挥关键作用。在这里，我们报告 RSK2 磷酸化半胱天冬酶-8，并且鉴定 Thr-263 为半胱天冬酶-8 的一个新磷酸化位点。此外，我们表明 EGF 通过蛋白酶体途径诱导半胱天冬酶-8 的泛素化和降解，并且 Thr-263 的磷酸化与半胱天冬酶-8 的稳定性相关。最后，RSK2 通过其对半胱天冬酶-8 的磷酸化来阻断 Fas 诱导的细胞凋亡。这些数据在 RSK2 和半胱天冬酶-8 之间提供了直接联系，并确定了 RSK2 对半胱天冬酶-8 调节的新分子机制。
