Heese K, Yamada T, Akatsu H, Yamamoto T, Kosaka K, Nagai Y, Sawada T
BF Research Institute, c/o National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-0873, Japan.
J Cell Biochem. 2004 Apr 1;91(5):1030-42. doi: 10.1002/jcb.20010.
Active cell death ('apoptosis' or 'programmed cell death') is essential in the development and homeostasis of multicellular organisms and abnormal inhibition of apoptosis is an indicator of cancer and autoimmune diseases, whereas excessive cell death might be implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Using bioinformatics-, Western-blotting-, yeast-two-hybrid-system-, polymerase chain reaction (PCR)-, and fluorescence microscopy-analyses, we demonstrate here that the neuroprotective protein p60TRP (p60-transcription-regulator-protein) is a basic helix-loop-helix (bHLH) domain-containing member of a new protein family that interacts with the Ran-binding-protein-5 (RanBP5) and the protein-phosphatase-2A (PP2A). The additional findings of its influence on NNT1 and p48ZnF (new-neurotrophin-1, p48-zinc-finger-protein)-signaling and its down-regulation in the brain of AD subjects point to a possible pivotal role of p60TRP in the control of cellular aging and survival.
细胞主动死亡(“凋亡”或“程序性细胞死亡”)在多细胞生物体的发育和内环境稳定中至关重要,凋亡的异常抑制是癌症和自身免疫性疾病的一个指标,而过度的细胞死亡可能与神经退行性疾病如阿尔茨海默病(AD)有关。通过生物信息学、蛋白质免疫印迹、酵母双杂交系统、聚合酶链反应(PCR)和荧光显微镜分析,我们在此证明神经保护蛋白p60TRP(p60转录调节蛋白)是一个新蛋白质家族中含有碱性螺旋-环-螺旋(bHLH)结构域的成员,它与Ran结合蛋白5(RanBP5)和蛋白磷酸酶2A(PP2A)相互作用。其对NNT1和p48ZnF(新神经营养因子-1,p48锌指蛋白)信号传导的影响以及在AD患者大脑中的下调等其他发现表明,p60TRP在细胞衰老和存活的控制中可能起关键作用。