Fkbp11-flox 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) and acts as a secretory translocon accessory factor, binding to ribosome-translocon complexes and acting on soluble secretory and transmembrane proteins during their synthesis at the endoplasmic reticulum (ER) [6]. It is transcriptionally regulated by XBP1s and is associated with important cellular processes such as cell growth through activation of the mechanistic target of rapamycin (mTOR) signaling [7].

In obese mice, restoring hepatic FKBP11 expression initiates an atypical UPR signaling pathway. This pathway 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, which may provide new treatment avenues for type 2 diabetes and obesity [1]. In hepatocellular carcinoma (HCC), FKBP11 is highly expressed. Knockdown of FKBP11 in HCC cells attenuates proliferation and migration, suggesting its role in HCC development and its potential as a diagnostic and prognostic marker [2]. In osteosarcoma, FKBP11 is highly expressed, and silencing its expression suppresses cell invasion, migration, and proliferation, while promoting apoptosis, and it may act 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, FKBP11 protects intestinal epithelial cells against inflammation-induced apoptosis by inhibiting the ER stress-associated JNK/caspase apoptotic pathway [5].

In conclusion, FKBP11 plays diverse roles in multiple biological processes and disease conditions. Studies using gene-knockout or knockdown models in various diseases like type 2 diabetes, obesity, different types of cancers, and Crohn's disease have revealed its functions in regulating UPR signaling, cell proliferation, migration, apoptosis, and inflammation. These findings contribute to understanding disease mechanisms and may guide the development of novel therapeutic strategies.