Peroxisomal matrix proteins are imported into peroxisomes via membrane-bound docking/translocation machinery. One central component of this machinery is Pex14p, a peroxisomal membrane protein involved in the docking of Pex5p, the receptor for peroxisome targeting signal type 1 (PTS1). Studies in several yeast species have shown that Pex14p is phosphorylated in vivo, whereas no function has been assigned to Pex14p phosphorylation in yeast and mammalian cells. Here, we investigated peroxisomal protein import and its dynamics in mitotic mammalian cells. In mitotically arrested cells, Pex14p is phosphorylated at Ser-232, resulting in a lower import efficiency of catalase, but not the majority of proteins including canonical PTS1 proteins. Conformational change induced by the mitotic phosphorylation of Pex14p more likely increases homomeric interacting affinity and suppresses topological change of its N-terminal part, thereby giving rise to the retardation of Pex5p export in mitotic cells. Taken together, these data show that mitotic phosphorylation of Pex14p and consequent suppression of catalase import are a mechanism of protecting DNA upon nuclear envelope breakdown at mitosis.

中文翻译：

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Pex14p 有丝分裂磷酸化调节过氧化物酶体输入机制

过氧化物酶体基质蛋白通过膜结合对接/易位机制导入过氧化物酶体。该机制的一个核心组件是 Pex14p，一种过氧化物酶体膜蛋白，参与 Pex5p 的对接，Pex5p 是过氧化物酶体靶向信号 1 型 (PTS1) 的受体。对几种酵母物种的研究表明，Pex14p 在体内被磷酸化，而在酵母和哺乳动物细胞中，Pex14p 磷酸化没有任何功能。在这里，我们研究了有丝分裂哺乳动物细胞中的过氧化物酶体蛋白输入及其动态。在有丝分裂停滞的细胞中，Pex14p 在 Ser-232 位点被磷酸化，导致过氧化氢酶的导入效率较低，但包括经典 PTS1 蛋白在内的大多数蛋白质则不然。Pex14p 有丝分裂磷酸化诱导的构象变化更有可能增加同聚体相互作用亲和力并抑制其 N 末端部分的拓扑变化，从而导致有丝分裂细胞中 Pex5p 输出的延迟。总而言之，这些数据表明 Pex14p 的有丝分裂磷酸化和随后的过氧化氢酶输入抑制是有丝分裂时核膜破裂时保护 DNA 的机制。