Selvakumar Ponniah, Lakshmikuttyamma Ashakumary, Charavaryamath Chandrashekhar, Singh Baljit, Tuchek John, Sharma Rajendra K
Department of Pathology, College of Medicine and Health Research Division, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 4H4.
Biochem Biophys Res Commun. 2005 Oct 7;335(4):1132-9. doi: 10.1016/j.bbrc.2005.07.190.
N-Myristoylation is a co-translational, irreversible addition of a fatty acyl moiety to the amino terminus of many eukaryotic cellular proteins. This modification is catalyzed by N-myristoyltransferase (NMT) and is recognized to be a widespread and functionally important modification of proteins. The myristoylated Src family kinases are involved in various signaling cascades, including the N-methyl-d-aspartate receptor functions. We examined the expression of NMT and its interacting proteins to gain further insight into the mechanisms in epileptic fowl. Higher expression of NMT1 and NMT2 was observed in carrier and epileptic fowl whereas expression of heat shock cognate protein 70, an inhibitor of NMT, was lower. Furthermore, protein-protein interaction of NMT with m-calpain, caspase-3, and p53 was established. The interaction of NMT2 with caspase-3 and p53 was weak in epileptic fowl compared with normal chicks while the interaction of NMT1 with m-calpain was weak in epileptics. Understanding the regulation of NMT by specific inhibitors may help us to control the action of this enzyme on its specific substrates and may lead to improvements in the management of various neurological disorders like Alzheimer's disease, ischemia, and epilepsy.
N-肉豆蔻酰化是一种共翻译过程，它将一个脂肪酰基部分不可逆地添加到许多真核细胞蛋白质的氨基末端。这种修饰由N-肉豆蔻酰转移酶（NMT）催化，并且被认为是一种广泛存在且在功能上很重要的蛋白质修饰。肉豆蔻酰化的Src家族激酶参与各种信号级联反应，包括N-甲基-D-天冬氨酸受体功能。我们检测了NMT及其相互作用蛋白的表达，以进一步深入了解癫痫鸡的发病机制。在携带癫痫基因的鸡和癫痫鸡中观察到NMT1和NMT2的表达较高，而NMT的抑制剂热休克同源蛋白70的表达较低。此外，还确定了NMT与m-钙蛋白酶、半胱天冬酶-3和p53之间的蛋白质-蛋白质相互作用。与正常雏鸡相比，癫痫鸡中NMT2与半胱天冬酶-3和p53的相互作用较弱，而癫痫患者中NMT1与m-钙蛋白酶的相互作用较弱。了解特定抑制剂对NMT的调节作用可能有助于我们控制该酶对其特定底物的作用，并可能改善对各种神经疾病（如阿尔茨海默病、局部缺血和癫痫）的治疗。
