Research Advances of Inner Nuclear Membrane-Associated Degradation
ZHANG Yutian, ZANG Yi*
In eukaryotes, nuclear emvelope is composed of two lipid bilayers, which distinguishs eukaryotes from prokaryotes. ONM (outer nuclear membrane) is continuous with endoplasmic reticulum. INM (inner nuclear membrane) is a specialized compartment with a unique proteome. ONM and INM are separated by nuclear pore complex. Recently, INMAD (inner nuclear membrane-associated degradation) has come into sight as a new pathway for protein quality control in nucleus. Ubiquitin-proteasome system is the most common mechanism for INMAD. INMAD not only degrades misfolded or mislocalized protein in nucleus, but also affects the distribution of INM protein. Current knowledge indicates that INMAD has some similarities to ERAD (endoplasmic reticulum-associated degradation). The mechanism of ERAD has been extensively studied, while INMAD pathway remains to be further elucidated. Herein, three branches of INMAD mediated by three E3 ubiquitin ligases were discussed, including Asi1/3, Doa10 and APC/C. They are different in canonical substrates, substrate recognition signals and the subsequent processes of ubiquitnation and degradation. Futhermore, INMAD is important in INM homeostasis. With the further study of INMAD, it may provide new strategies for discoveries and treatments of INM-related diseases.
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