Rathaus Moran, Lerrer Batya, Cohen Haim Y
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Cell Cycle. 2009 Jun 15;8(12):1843-52. doi: 10.4161/cc.8.12.8864. Epub 2009 Jun 27.
The Ku70 protein was shown to be involved in multiple cellular pathways including DNA repair, telomere maintenance, V(D)J recombination and Bax mediated apoptosis. Yet, despite this wide spectrum of pathways, until recently the enzymatic activity of Ku70 was elusive. Recent findings demonstrate that Ku70 is associated with the proapoptotic protein Bax and possesses a deubiquitin enzyme (DUB) activity on it. These data suggest a dual role for Ku70 in apoptotic regulation; on one hand the association with Ku70 sequestered Bax away from the mitochondria and plays an antiapoptotic function. On the other hand, this association mediates and promotes Bax deubiquitylation which will block its labeling for proteasomal degradation and in this manner Ku70 will have a proapoptotic role. The exciting finding of Ku70's DUB activity opens numerous avenues for future research. Here we suggest candidate substrate proteins and indicate how the DUB activity of Ku70 on these, might affect the known Ku70's related pathways.
Ku70蛋白被证明参与多种细胞途径，包括DNA修复、端粒维持、V(D)J重组以及Bax介导的细胞凋亡。然而，尽管涉及如此广泛的途径，但直到最近Ku70的酶活性仍不清楚。最近的研究结果表明，Ku70与促凋亡蛋白Bax相关，并对其具有去泛素酶（DUB）活性。这些数据表明Ku70在细胞凋亡调控中具有双重作用；一方面，与Ku70的结合使Bax远离线粒体，发挥抗凋亡功能。另一方面，这种结合介导并促进Bax去泛素化，从而阻止其被标记用于蛋白酶体降解，通过这种方式Ku70将发挥促凋亡作用。Ku70具有DUB活性这一令人兴奋的发现为未来的研究开辟了众多途径。在此我们提出候选底物蛋白，并指出Ku70对这些蛋白的DUB活性可能如何影响已知的与Ku70相关的途径。
