有研究表明，特异性抑制p97会引起多聚泛素化蛋白的聚集、ERAD底物的滞留和无法解决的蛋白毒性应激，导致未折叠蛋白响应的凋亡通路的激活，最终发挥治疗癌症的作用（Targeting the AAA ATPase p97 as an approach to treat cancer through disruption of protein homeostasis）。

2023年8月1日 · ERAD represents a collection of independent processes exhibiting distinct yet overlapping selectivity for a wide range of substrates, enabling efficient quality control of membrane and secretory...

2023年10月13日 · We determined the cryo-EM structures of the hetero-decameric complex formed by the Derlin-1 tetramer and the p97 hexamer. It showed an intriguing asymmetric complex and a putative coordinated squeezing movement in Derlin-1 and p97 parts.

2023年2月6日 · We show that the p97 AAA-ATPase and its adaptor ubiquitin-X domain adaptor 8 (UBXD8) regulate ERMCS. The p97-UBXD8 complex localizes to contacts and its loss increases contacts in a manner that...

2021年3月17日 · In the ERAD pathway, p97 functions as a molecular ratchet, pulling the ubiquitinated, unfolded proteins from the ER for proteasomal degradation in the cytosol 5. Many types of cancers express...

A newly identified VIM (p97/VCP-interacting motif) in gp78 has brought about novel insights into mechanisms of ERAD, such as the presence of a p97/VCP-dependent but Ufd1-independent retrotranslocation during gp78-mediated ERAD. Additionally, SVIP (small p97/VCP-interacting protein), which contains a VIM in its N-terminal region, negatively ...

2006年5月19日 · ERAD impairment resulted from the direct loss of p97/VCP activity due to the assembly of dysfunctional (dominant-negative) hexamers, as confirmed by gene silencing of endogenous p97/VCP with a short-hairpin RNA (shRNA) (Table 1). It is important to note that high expression levels of some p97/VCP mutants (particularly those in the D2 domain ...

Quality control mechanisms in the endoplasmic reticulum prevent deployment of aberrant or unwanted proteins to distal destinations and target them to degradation by a process known as endoplasmic reticulum-associated degradation, or ERAD. Attempts to characterize ERAD by identifying a specific compo …

2020年3月12日 · The AAA+ ATPase, p97, also referred to as VCP, plays an essential role in cellular homeostasis by regulating endoplasmic reticulum-associated degradation (ERAD), mitochondrial-associated degradation (MAD), chromatin-associated degradation, autophagy, and endosomal trafficking. Mutations in p97 have …

2015年11月9日 · Treatment of tumor cells with CB-5083 leads to accumulation of poly-ubiquitinated proteins, retention of endoplasmic reticulum-associated degradation (ERAD) substrates, and generation of irresolvable proteotoxic stress, leading to activation of the apoptotic arm of the unfolded protein response.