Fkbp11-KO Mouse

Fkbp11, also known as FK506-binding protein 11, is a member of the peptidyl-prolyl cis-trans isomerase family. It is involved in the unfolded protein response (UPR) pathway and acts as a translocon accessory factor during the synthesis of soluble secretory and transmembrane proteins at the endoplasmic reticulum (ER) [6]. It also has connections to various biological processes such as cell growth, proliferation, and apoptosis, making it biologically important in understanding disease mechanisms.

In obese mice, restoring hepatic Fkbp11 expression initiates an atypical UPR signaling pathway. It rewires PERK signaling toward NRF2, away from the eIF2α-ATF4 axis of the UPR, establishing glucose homeostasis without changing hepatic ER stress, food consumption, or body weight. This indicates that Fkbp11 could be a potential target to treat type 2 diabetes and obesity related to ER stress [1].

In hepatocellular carcinoma (HCC), Fkbp11 is upregulated, and knockdown of Fkbp11 in HCC cells attenuates proliferation and migration, suggesting its role in HCC pathogenesis. Its levels are significantly reduced post-surgery, making it a potential diagnostic and prognostic marker for HCC [2].

In osteosarcoma, Fkbp11 is highly expressed, and silencing its expression suppresses cell invasion, migration, slows proliferation, and promotes apoptosis through the MAPK pathway [3].

In oral squamous cell carcinoma (OSCC), FKBP11 promotes cell proliferation by regulating the G2/M phase and apoptosis via p53-related pathways [4].

In Crohn's disease, increased FKBP11 expression in intestinal inflammatory tissues protects intestinal epithelial cells against inflammation-induced apoptosis via the JNK-caspase pathway [5].

In conclusion, Fkbp11 plays crucial roles in multiple biological processes and disease conditions. Model-based research, especially using gene knockout or conditional knockout mouse models, has revealed its significance in diseases like type 2 diabetes, obesity, and various cancers. Understanding Fkbp11's functions provides potential targets for developing novel therapeutic strategies for these diseases.