Misfolded proteins of the endoplasmic reticulum (ER) are discarded by a conserved process, called ER-associated protein degradation (ERAD). ERAD substrates are retro-translocated into the cytosol, polyubiquitinated, extracted from the ER …

Distinct endoplasmic reticulum-associated degradation (ERAD) pathways. Three main ERAD pathways in yeast are classified based on substrates and the components that are involved in their degradation. ERAD-L degrades membrane integrated or soluble proteins with misfolded domains in the ER lumen, marked with (L).

2014年2月7日 · Deubiquitinating enzymes (DUBs) regulate various cellular processes ranging from protein degradation to cellular signaling. USP19, the only DUB containing a carboxyl-terminal transmembrane domain, was proposed to function in endoplasmic reticulum-associated degradation (ERAD). Here we characterize the function and regulation of USP19.

Surprisingly, recent studies have revealed an equally important function for deubiquitinases (DUBs), enzymes that disassemble ubiquitin chains, in ERAD. Intriguingly, many ERAD specific DUBs are physically associated with the retrotranslocation-driving ATPase p97.

2019年11月12日 · If the Hrd1 channel is activated by autoubiquitination, how is Hrd1 spared from degradation and returned to its inactive ground state? Here, we identify Ubp1 as a membrane-bound deubiquitinating enzyme (DUB) that reverses the polyubiquitin modification of Hrd1 and allows Hrd1 to escape uncontrolled degradation.

2021年8月1日 · DUBs function as modulators in a variety of neurodegenerative diseases. DUBs regulate toxic proteins inducing neurodegenerative diseases via proteasome signaling, mitophagy, autophagy, and ERAD. DUB small molecule inhibitors affect the targeted toxic proteins related to neurodegenerative diseases via decomposition mechanism.

2014年9月11日 · Recent experiments have also implicated deubiquitinating enzymes (DUBs) in ERAD (for review, see Liu and Ye, 2012). Several DUBs associate with Cdc48p or its mammalian homolog p97, and the overexpression of dominant-negative forms blocks ERAD in mammalian cells. However, it remains unclear how DUBs participate in ERAD.

2023年8月1日 · ERAD serves two principal physiological roles: first, protection against the accumulation of defective, slow-folding or unfolding proteins that might otherwise be toxic and impede secretory...

泛素一蛋白酶体途径 （ubiquitin-proteasome pathway）是细胞内一个重要的蛋白质降解调节系统。 通过对底物蛋白的多聚泛素化并经蛋白酶体降解，可以影响或调节多种细胞活动，包括：基因转录、细胞周期调节、免疫反应、细胞受体功能及肿瘤生长、炎症过程等。 该途径也是一种动态的蛋白质双向修饰调控系统，在体内由 泛素连接酶系统 （E1-E2-E3）对底物进行泛素化修饰，去泛素化酶（DUB）家族负责通过水解泛素羧基末端的酯键、肽键或异肽键，将泛素分子特异性的从 …

2023年6月29日 · ER-associated degradation (ERAD) is one of the protein quality and quantity control system located at ER, which is responsible for translocating the misfolded proteins or properly folded but excess proteins out of the ER for proteasomal degradation.