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首页> 外文期刊>Molecular and Cellular Biology >N-Terminal Ubiquitination of Extracellular Signal-Regulated Kinase 3 and p21 Directs Their Degradation by the Proteasome
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N-Terminal Ubiquitination of Extracellular Signal-Regulated Kinase 3 and p21 Directs Their Degradation by the Proteasome

机译：N端泛素化的胞外信号调节激酶3和p21指导他们降解的蛋白酶体。

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Extracellular signal-regulated kinase 3 (ERK3) is an unstable mitogen-activated protein kinase homologue that is constitutively degraded by the ubiquitin-proteasome pathway in proliferating cells. Here we show that a lysineless mutant of ERK3 is still ubiquitinated in vivo and requires a functional ubiquitin conjugation pathway for its degradation. Addition of N-terminal sequence tags of increasing size stabilizes ERK3 by preventing its ubiquitination. Importantly, we identified a fusion peptide between the N-terminal methionine of ERK3 and the C-terminal glycine of ubiquitin in vivo by tandem mass spectrometry analysis. These findings demonstrate that ERK3 is conjugated to ubiquitin via its free NH2 terminus. We found that large N-terminal tags also stabilize the expression of the cell cycle inhibitor p21 but not that of substrates ubiquitinated on internal lysine residues. Consistent with this observation, lysineless p21 is ubiquitinated and degraded in a ubiquitin-dependent manner in intact cells. Our results suggests that N-terminal ubiquitination is a more prevalent modification than originally recognized.
机译：细胞外信号调节激酶3（ERK3）是一种不稳定的促分裂原活化蛋白激酶同源物，在增殖细胞中被泛素-蛋白酶体途径组成性降解。在这里，我们显示ERK3的无赖氨酸突变体仍在体内泛素化，并且需要功能性的泛素结合途径对其进行降解。增加大小增加​​的N末端序列标签可通过阻止ERK3泛素化来稳定ERK3。重要的是，我们通过串联质谱分析在体内鉴定了ERK3的N末端甲硫氨酸与泛素的C末端甘氨酸之间的融合肽。这些发现表明ERK3通过其游离的NH 2 末端与泛素缀合。我们发现大的N末端标签还可以稳定细胞周期抑制剂p21的表达，但不能稳定内部赖氨酸残基上泛素化的底物的表达。与该观察结果一致，无赖氨酸的p21在完整细胞中被泛素化并以泛素依赖性方式降解。我们的结果表明，N端泛素化是比最初公认的更普遍的修饰。

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