Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators
Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators
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DOI：
10.1016/j.celrep.2016.10.078
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发表时间：
2016-11-22
期刊：
影响因子：
8.8
通讯作者：
Gingras, Anne-Claude
中科院分区：
文献类型：
--
作者：
St-Denis, Nicole;Gupta, Gagan D.;Gingras, Anne-Claude
可逆磷酸化是一种基本的调节机制，由激酶和磷酸酶复杂地协调，这两类酶在人类疾病中被广泛破坏。为了更好地了解相对未被充分研究的磷酸酶的功能，我们使用了互补亲和纯化和基于邻近相互作用的蛋白质组学方法，为140种含有磷酸酶催化结构域的人类蛋白质生成了物理相互作用组。我们确定了1335种高可信度相互作用（1104种以前未报道），暗示这些磷酸酶参与各种细胞过程的调节。磷酸酶催化和调控亚基的系统表型分析揭示了来自每个进化家族的磷酸酶对有丝分裂的影响。利用相互作用组的线索，我们发现了DUSP19在有丝分裂退出、CDC14A在调节微管完整性、PTPRF在有丝分裂收缩纤维完整性以及DUSP23在中心粒复制中的意想不到的作用。功能性磷酸酶相互作用组进一步为这类重要酶的功能归属提供了丰富的资源。
Reversible phosphorylation is a fundamental regulatory mechanism, intricately coordinated by kinases and phosphatases, two classes of enzymes widely disrupted in human disease. To better understand the functions of the relatively understudied phosphatases, we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains. We identified 1,335 high-confidence interactions (1,104 previously unreported), implicating these phosphatases in the regulation of a variety of cellular processes. Systematic phenotypic profiling of phosphatase catalytic and regulatory subunits revealed that phosphatases from every evolutionary family impinge on mitosis. Using clues from the interactome, we have uncovered unsuspected roles for DUSP19 in mitotic exit, CDC14A in regulating microtubule integrity, PTPRF in mitotic retraction fiber integrity, and DUSP23 in centriole duplication. The functional phosphatase interactome further provides a rich resource for ascribing functions for this important class of enzymes.