Alpha4 is an essential regulator of PP2A phosphatase activity.
Alpha4 is an essential regulator of PP2A phosphatase activity.
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α4是PP2A磷酸酶活性的必不可少的调节剂。
DOI：
10.1016/j.molcel.2009.09.025
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发表时间：
2009-10-09
期刊：
影响因子：
16
通讯作者：
Thompson, Craig B.
中科院分区：
文献类型：
--
作者：
Kong, Mei;Ditsworth, Dara;Lindsten, Tullia;Thompson, Craig B.
丝氨酸/苏氨酸磷酸酶的活性和特异性很大程度上受其相关蛋白的控制。α4是PP 2A样磷酸酶进化上保守的非催化亚基。虽然α4仅与少数PP 2A相关催化亚基结合，但α4缺失导致所有PP 2A、PP 4和PP 6磷酸酶复合物的进行性丧失。在健康细胞中，与α4的结合使催化（C）亚基在酶促作用下失活，同时保护它们免受蛋白酶体降解，直到它们组装成功能性磷酸酶复合物。在细胞应激期间，现有的PP 2A复合物可能变得不稳定。在这种条件下，α4螯合释放的C亚基，并且是适应性增加靶向PP 2A活性所必需的，该活性可以使应激诱导的磷酸化底物去磷酸化。与此一致，α4的过表达保护细胞免受各种应激刺激，包括DNA损伤和营养限制。这些发现表明，α4在调节适应性PP 2A磷酸酶复合物的组装和维持中起着必要的作用。
The activity and specificity of serine/threonine phosphatases is governed largely by their associated proteins. α4 is an evolutionarily conserved non-catalytic subunit for PP2A-like phosphatases. While α4 binds to only a minority of PP2A-related catalytic subunits, α4 deletion leads to progressive loss of all PP2A, PP4, and PP6 phosphatase complexes. In healthy cells, association with α4 renders catalytic (C) subunits enzymatically inactive while protecting them from proteasomal degradation until they are assembled into a functional phosphatase complex. During cellular stress, existing PP2A complexes can become unstable. Under such conditions, α4 sequesters released C subunits and is required for the adaptive increase in targeted PP2A activity that can dephosphorylate stress-induced phosphorylated substrates. Consistent with this, overexpression of α4 protects cells from a variety of stress stimuli, including DNA damage and nutrient limitation. These findings demonstrate that α4 plays a required role in regulating the assembly and maintenance of adaptive PP2A phosphatase complexes.
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