Vcp-flox Mouse

Vcp, also known as p97, is an evolutionarily conserved AAA+ ATPase crucial for cellular homeostasis. It is involved in multiple cellular processes including the ubiquitin-proteasome system, autophagy/lysosomal route, and endoplasmic-reticulum-associated degradation pathway, which are essential for maintaining protein homeostasis [4,5].

In hepatocellular carcinoma (HCC), Vcp expression is increased in tumor tissues, promoting cell proliferation, migration, and invasion via the PI3K/AKT/mTOR pathway activation. Knockdown of Vcp leads to reverse phenotypes, indicating its oncogenic role [1].

In Vcp-related myopathy, dominant missense mutations in the Vcp gene can cause a muscular phenotype without central nervous system involvement [2]. Regarding autophagy, Vcp UFMylation stabilizes BECN1, facilitating autophagy initiation. Pathogenic Vcp mutations in neurological disorders and cancers are associated with reduced UFMylation [3].

In conclusion, Vcp is a key regulator in maintaining cellular proteostasis, with its functions extending to various biological processes and disease conditions. Research using gene-related models such as knockdown in HCC and mutation-associated myopathy cases has revealed its roles in cancer progression and muscle-related diseases, highlighting its potential as a therapeutic target in these areas.