Regulation of peroxisomal protein import by modification of cysteine residue

过氧化物酶体是包含多种代谢途径的重要细胞器，通过选择性地将蛋白质输入过氧化物酶体来保证生理功能。Pex5p是过氧化物酶体靶向信号1型的胞质受体，在过氧化物酶体基质蛋白的输入中起关键作用。本研究阐明了Pex5p被三种不同的泛素化模式修饰，即半胱氨酸连接的单泛素化和两种赖氨酸连接的单泛素化。Pex5p泛素化是Pex5p从过氧化物酶体膜输出到细胞质及其补充活性的先决条件。另一方面，Pex5p在多个赖氨酸残基上的单泛素化确保了过氧化物酶体中Pex5p的有效输出。Pex5p在Lys520位点的单泛素化可能在胞浆中自抑制Pex5p的货物识别中起作用。因此，过氧化物酶体基质蛋白的输入是由Pex5p独特的泛素修饰精心调节的。

Peroxisome is an essential organelle containing various metabolic pathways and the physiological functions are assured by selective protein import into peroxisomes. Pex5p, a cytosolic receptor of peroxisome targeting signal type-1, plays a pivotal role in peroxisome matrix protein import.This study clarified that Pex5p is modified by three distinct modes of ubiquitination, a cysteine-linked monoubiquitination and two types of lysine-linked monoubiquitination. Cys-linked ubiquitination of Pex5p is prerequisite for export of Pex5p from peroxisomal membrane to the cytosol and its complementing activity. On the other hand, monoubiquitination of Pex5p at multiple lysine residues ensures the efficient export of Pex5p from peroxisomes. Monoubiquitination of Pex5p at Lys520 in vivo might play a role in self-inhibition of Pex5p in the cargo recognition in the cytosol. Therefore, import of peroxisome matrix proteins is elaborately regulated by unique ubiquitin modifications of Pex5p.