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首页> 外文期刊>The FEBS journal >An alternative transcript from the death-associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing
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An alternative transcript from the death-associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing

机译：来自死亡相关蛋白激酶1基因座的替代转录本，编码一种小蛋白，选择性介导膜起泡

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Death-associated protein kinase 1 (DAPK-1) is a multidomain protein kinase with diverse roles in autophagic, apoptotic and survival pathways. Bioinformatic screens were used to identify a small internal mRNA from the DAPK-1 locus (named s-DAPK-1). This encodes a 295 amino acid polypeptide encompassing part of the ankyrin-repeat domain, the P-loop motifs, part of the cytoskeletal binding domain of DAPK-1, and a unique C-terminal 'tail' extension not present in DAPK-1. Expression of s-DAPK-1 mRNA was detected in a panel of normal human tissues as well as primary colorectal cancers, indicating that its expression occurs in vivo. s-DAPK-1 gene transfection into cells produces two protein products: one with a denatured mass of 44 kDa, and a smaller product of 40 kDa. Double alanine mutation of the C-terminal tail extension of s-DAPK-1 (Gly296/Arg297) prevented production of the 40 kDa fragment, suggesting that the smaller product is generated by in vivo proteolytic processing. The s-DAPK-1 gene cannot substitute for full-length DAPK-1 in an mitogen-activated protein kinase kinase/extracellular signal-regulated kinase-dependent apoptotic transfection assay. However, the transfection of s-DAPK-1 was able to mimic full-length DAPK-1 in the induction of membrane blebbing. The 44 kDa protease-resistant mutant s-DAPK-1G296A/R297A had very low activity in membrane blebbing, whereas the 40 kDa s-DAPK-1 Delta tail protein exhibited the highest levels of membrane blebbing. Deletion of the tail extension of s-DAPK-1 increased its half-life, shifted the equilibrium of the protein from cytoskeletal to soluble cytosolic pools, and altered green fluorescent protein-tagged s-DAPK-1 protein localization as observed by confocal microscopy. These data highlight the existence of an alternative product of the DAPK-1 locus, and suggest that proteolytic removal of the C-terminal tail of s-DAPK-1 is required to stimulate maximally its membrane-blebbing function.
机译：死亡相关蛋白激酶1（DAPK-1）是一种多域蛋白激酶，在自噬，凋亡和存活途径中具有多种作用。使用生物信息学筛选技术从DAPK-1基因座（名为s-DAPK-1）中鉴定出小的内部mRNA。它编码一个295个氨基酸的多肽，包括锚蛋白重复结构域的一部分，P环基序，DAPK-1的细胞骨架结合结构域的一部分以及DAPK-1中不存在的独特的C端“尾部”延伸。在一组正常人组织以及原发性结肠直肠癌中检测到s-DAPK-1 mRNA的表达，表明其表达发生在体内。 s-DAPK-1基因转染入细胞会产生两种蛋白质产物：一种具有44 kDa的变性质量，另一种具有40 kDa的变性产物。 s-DAPK-1（Gly296 / Arg297）的C末端尾部延伸的双丙氨酸突变阻止了40 kDa片段的产生，这表明较小的产物是通过体内蛋白水解过程产生的。在有丝分裂原激活的蛋白激酶激酶/细胞外信号调节激酶依赖性凋亡转染试验中，s-DAPK-1基因不能替代全长DAPK-1。但是，s-DAPK-1的转染能够模拟全长DAPK-1诱导膜起泡。耐44 kDa蛋白酶的突变体s-DAPK-1G296A / R297A在膜起泡中具有非常低的活性，而40 kDa s-DAPK-1 Delta尾蛋白表现出最高的膜起泡水平。通过共聚焦显微镜观察，删除s-DAPK-1的尾巴延长段可延长其半衰期，将蛋白质的平衡从细胞骨架转移至可溶性胞质池，并改变了带有绿色荧光蛋白标签的s-DAPK-1的蛋白质定位。这些数据突出显示了DAPK-1基因座的另一种产物的存在，并表明需要蛋白水解去除s-DAPK-1的C末端尾部以最大程度地刺激其膜起泡功能。

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