期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 111, 期 5, 页码 1359-1366出版社
WILEY
DOI: 10.1002/jcb.22864
关键词
CYCLIN-DEPENDENT KINASE-5; ALZHEIMER'S DISEASE; NEURODEGENERATION; NEURONAL DEATH; P35; P10
资金
- National Medical Research Council of Singapore [R-183-000-075-213, 183-000-079-213]
- National University of Singapore [R-183-000-060-214]
- Research Grants Council of Hong Kong [HKUST6128/04M]
- University Grants Committee of Hong Kong [AoE/B-15/01]
- Strategic Initiative Funding (Menzies Research Institute)
The involvement of cyclin-dependent kinase-5 (Cdk5) and p25, the proteolytic fragment of activator p35, has long been implicated in the development of neuron-fibrillary tangles (NFTs), a hallmark of Alzheimer's disease (AD). Findings in this area over the past decade have been highly controversial and inconclusive. Here we report unprecedented detection of endogenous p10, the smaller proteolytic fragment of the Cdk5 activator p35 in treated primary cortical neurons that underwent significant apoptosis, triggered by proteasome inhibitors MG132 and lactacystin, and protein kinase inhibitor staurosporine (STS). p10 appeared exclusively in the detergent-resistant fraction made up of nuclear matrix, membrane-bound organelles, insoluble membrane proteins, and cytoskeletal components. Intriguingly, transient overexpression of p10 in neural cells induced apoptotic morphologies, suggesting that p10 may play an important role in mediating neuronal cell death in neurodegenerative diseases. We demonstrated for the first time that p10-mediated apoptosis occurred via a caspases-independent pathway. Furthermore, as p10 may contain the myristoylation signal for p35 which is responsible for binding p35 to several intracellular components and the membrane, all in all these novel results present that the accumulation of p10 to the detergent-insoluble fraction may be a crucial pathological event to triggering neuronal cell death. J. Cell. Biochem. 111: 1359-1366, 2010. (C) 2010 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据