塔斯帕酶1:一种需要用于MLL分裂和适当的HOX基因表达的三氨酸阿斯巴达酶
James J-D Hsieh1, Emily H-Y Cheng, Stanley J Korsmeyer
1Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell
|November 26, 2003
概括
研究人员确定了Taspase1,这是一种关键蛋白酶,用于分裂混合血统白血病 (MLL) 蛋白质. 这种裂变对于维持HOX基因表达和正常发育至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 混合血统白血病 (MLL) 基因对于HOX基因表达至关重要,同类于Drosophila trithorax.
- MLL蛋白质经历裂变成N320和C180碎片,这些碎片异构为稳定性和亚核定位.
研究的目的:
- 识别和克隆负责分裂MLL蛋白的蛋白酶.
- 为了描述这个MLL分裂蛋白酶的功能和进化起源.
主要方法:
- 净化和克隆MLL分裂蛋白酶.
- 蛋白酶的酶活性和结构的表征.
- RNA干扰 (RNAi) 来评估蛋白酶敲除对MLL处理和HOX基因表达的影响.
主要成果:
- 这种蛋白质酶被确定为Taspase1,它是一种利用N-终端三氨酸核的内皮酶.
- 塔斯巴酶1经历了分子内裂变,形成一个活跃的α/β异构体.
- 塔斯帕酶1的淘汰导致未经处理的MLL,并破坏了HOX基因表达.
结论:
- 塔斯巴酶1对于MLL处理和随后的HOX基因调节至关重要.
- 塔斯帕酶1与MLL的共同进化表明它在更高的生物体中开发复杂的身体计划中的作用.
- 塔斯巴酶1代表了一种新型的蛋白酶类别,其始发与N端的三氨酸.
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