Greenwood J, Gautier J
Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University Medical Center, New York, NY 10032, USA.
Cell Death Differ. 2007 Mar;14(3):559-67. doi: 10.1038/sj.cdd.4402031. Epub 2006 Sep 29.
The balance between proliferation and cell death is critical for embryonic development and adult tissue homeostasis. Within an individual cell, coordination of these pathways is aided by direct communication between cell cycle factors and molecules that regulate apoptosis. Here, we show that XLX, a Xenopus laevis inhibitor of apoptosis (IAP) family member, exhibits characteristics typical of an IAP, such as caspase inhibition and autoubiquitylation. However, unlike other IAPs described thus far, we found that XLX is phosphorylated during meiosis by protein kinases that belong to the MAPK and MPF pathways. Finally, we show that caspase-dependent cleavage of XLX is altered when XLX is phosphorylated. In addition to furthering our understanding of the post-translational regulation of an IAP, these findings reveal a novel link between cell cycle-regulated protein kinases and a component potentially involved in apoptosis.
增殖与细胞死亡之间的平衡对于胚胎发育和成年组织稳态至关重要。在单个细胞内，细胞周期因子与调节细胞凋亡的分子之间的直接通讯有助于这些途径的协调。在这里，我们表明非洲爪蟾凋亡抑制蛋白（IAP）家族成员XLX具有IAP的典型特征，如半胱天冬酶抑制和自身泛素化。然而，与迄今为止描述的其他IAP不同，我们发现XLX在减数分裂期间被属于MAPK和MPF途径的蛋白激酶磷酸化。最后，我们表明当XLX被磷酸化时，其依赖半胱天冬酶的切割会发生改变。除了加深我们对IAP翻译后调控的理解之外，这些发现还揭示了细胞周期调节的蛋白激酶与可能参与细胞凋亡的一个组分之间的新联系。
