Accumulating evidence suggests that STAT-mediated signaling plays critical roles in cell differentiation and/or cell expansion and that in turn, STAT-mediated signaling is regulated strictly by many mechanisms. In murine mast cells, when Stat6 is activated by IL-4 and translocated to the nucleus, Stat6 is cleaved by a nucleus-associated protease (namely Stat6-protease). Similarly, the activated Stat5 is cleaved by a protease (Stat5-protease) in the nucleus of myeloid progenitors. These STAT proteases cleave the corresponding STAT proteins at the carboxyl-terminus and the resultant STAT proteins function as dominant negative molecules. Functionally, Stat6-protease protects mast cells from Stat6-dependent growth inhibition while Stat5-protease maintains the immature state of myeloid progenitors. In addition, it has been shown that the activated Stat3 is cleaved in mature neutrophils. These findings indicate that the proteolytic processing of STAT proteins by the nucleus-associated protease functions as a lineage-specific negative-regulator of STAT-mediated signaling.

中文翻译：

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通过蛋白水解过程对STAT介导的信号传导的谱系特异性负调节。

越来越多的证据表明，STAT介导的信号传导在细胞分化和/或细胞扩增中起着关键作用，而STAT介导的信号传导又受许多机制的严格调控。在鼠肥大细胞中，当Stat6被IL-4激活并转移到细胞核时，Stat6被细胞核相关蛋白酶（即Stat6-蛋白酶）裂解。类似地，活化的Stat5被髓样祖细胞核中的蛋白酶（Stat5-蛋白酶）切割。这些STAT蛋白酶在羧基末端切割相应的STAT蛋白，并且所得的STAT蛋白起显性负分子的作用。从功能上讲，Stat6蛋白酶可保护肥大细胞免受Stat6依赖性生长的抑制，而Stat5蛋白酶则可维持骨髓祖细胞的未成熟状态。此外，已经表明，活化的Stat3在成熟的嗜中性粒细胞中被裂解。这些发现表明，与细胞核相关的蛋白酶对STAT蛋白的蛋白水解过程起着STAT介导信号传导的谱系特异性负调节剂的作用。