PLK1 P53350

丝氨酸/苏氨酸蛋白激酶PLK1 (EC 2.7.11.21) (Polo样激酶1) (PLK-1) (丝氨酸/苏氨酸蛋白激酶13) (STPK13)

功能描述

丝氨酸/苏氨酸蛋白激酶，在细胞周期的M期执行多项重要功能，包括调控中心体成熟和纺锤体组装、从染色体臂上去除cohesin、失活后期促进复合物/环体 (APC/C) 抑制剂，以及调控有丝分裂退出和胞质分裂 (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084)。Polo样激酶蛋白通过结合并磷酸化已在特定基序上被磷酸化的蛋白起作用，该基序可被POLO box结构域识别 (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084)。磷酸化 BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 和 HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084)。通过磷酸化 KIZ, NEDD1 和 NINL，在中心体功能和双极纺锤体组装中发挥关键作用 (PubMed:16980960, PubMed:19509060)。NEDD1 磷酸化促进γ-微管蛋白环复合物 (gTuRC) 随后靶向中心体，这是纺锤体形成的重要步骤 (PubMed:19509060)。磷酸化中心体的 NINL 组分导致 NINL 与其他中心体蛋白解离 (PubMed:12852856)。通过磷酸化 CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 和 RACGAP1 参与有丝分裂退出和胞质分裂 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302)。通过磷酸化并停泊 PRC1 和 KIF20A/MKLP2 被募集到中央纺锤体；通过介导位点磷酸化在 PRC1 和 KIF20A/MKLP2 上产生自身的停泊位点，随后被 POLO box结构域识别 (PubMed:12939256, PubMed:17351640)。磷酸化 RACGAP1，从而为 Rho GTP交换因子 ECT2 创造停泊位点，这对分裂沟的形成至关重要 (PubMed:19468300, PubMed:19468302)。促进 ECT2 的中央纺锤体募集 (PubMed:16247472)。通过磷酸化 CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 和 WEE1，在有丝分裂细胞周期的 G2/M 期转换中发挥核心作用 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488)。作为调节回路的一部分，通过磷酸化正调节因子 CDC25C 并抑制负调节因子 WEE1 和 PKMYT1/MYT1 促进 CDK1 的激活 (PubMed:11202906)。还通过在前期介导中心体上的细胞周期蛋白B1 (CCNB1) 磷酸化起作用 (PubMed:12447691, PubMed:12524548)。磷酸化关键的有丝分裂转录调节因子 FOXM1，从而增强 FOXM1 的转录活性 (PubMed:19160488)。通过磷酸化 BUB1B/BUBR1, FBXO5/EMI1 和 STAG2/SA2 参与动粒功能和姐妹染色单体黏附 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714)。PLK1 在未附着动粒上高丰度存在，表明 PLK1 在动粒附着或纺锤体组装检查点 (SAC) 调控中起作用 (PubMed:17617734)。BUB1B 的动粒定位需要 PLK1 (PubMed:17376779)。通过磷酸化 cohesin 亚基如 STAG2/SA2 调控 cohesin 从染色体上的解离 (By similarity)。磷酸化 SGO1：SGO1 异构体 3 的纺锤体极定位需要该过程，并在调节其中心粒黏附功能中发挥作用 (PubMed:18331714)。介导 FBXO5/EMI1 的磷酸化，FBXO5/EMI1 是前期 APC/C 复合物的负调节因子，导致 FBXO5/EMI1 泛素化并被蛋白酶体降解 (PubMed:15148369, PubMed:15469984)。作为 p53 家族成员的负调节因子：磷酸化 TOPORS，导致抑制 p53/TP53 的类泛素化，同时增强 p53/TP53 的泛素化及随后的降解 (PubMed:19473992)。磷酸化转录因子 p73/TP73 的反式激活结构域，导致抑制 p73/TP73 介导的转录激活和促凋亡功能。磷酸化 BORA，从而促进 BORA 的降解 (PubMed:18521620)。有助于调节 AURKA 功能 (PubMed:18615013, PubMed:18662541)。也是 DNA 损伤检查点恢复和进入有丝分裂所必需的 (PubMed:18615013, PubMed:18662541)。磷酸化 MISP，导致稳定

组织特异性

Placenta and colon.

亚细胞定位

Nucleus. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome