Molecular mechanism underlying selective autophagy of aggregated protein

p62 在其泛素相关 (UBA) 结构域中的特异性磷酸化可调节多泛素化蛋白聚集体的自噬清除。 p62 的这种磷酸化形式以更高的亲和力与多聚泛素链结合，从而在作为自噬体进入单位的“sequestosomes”中有效地募集多聚泛素化蛋白。 p62 的磷酸化调节泛素化蛋白的自噬清除，而这些蛋白很难被蛋白酶体降解。

The specific phosphorylation of p62 in its ubiquitin-associated (UBA) domain, regulates the autophagic clearance of polyubiquitinated protein aggregate. This phosphorylated form of p62 binds to polyubiquitin chains with higher affinity, resulting in the efficient recruitment of polyubiquitinated proteins in the "sequestosomes" which are units of autophagosome entry. The phosphorylation in p62 regulates autophagic clearance of ubiquitinated proteins that are poorly degraded by proteasomes.