MsrB3, or methionine sulfoxide reductase B3, is a protein repair enzyme that specifically catalyzes the reduction of methionine-R-sulfoxide residues, thus having an antioxidant function [2,3]. It is involved in multiple biological pathways, and its role in maintaining cellular redox balance is of great biological importance. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its function.

In cancer research, MsrB3 deficiency has been shown to induce cancer cell apoptosis. In breast and colon cancer cells, MsrB3 depletion led to p53 down-regulation at the post-transcriptional level, but apoptosis occurred independently of p53. Instead, it was associated with increased endoplasmic reticulum (ER) stress. MsrB3 deficiency increased cytosolic calcium levels, disturbing calcium homeostasis in the ER and triggering ER stress. Also, it activated the pro-apoptotic Bim molecule, essential for ER stress-induced apoptosis [1]. In clear cell renal cell carcinoma (ccRCC), MSRB3 was up-regulated, and its knockdown arrested cell proliferation, migration, and invasion, while promoting apoptosis and inducing ER stress marker changes [2]. Additionally, in general cancer cell studies, MsrB3 depletion induced apoptosis through the activation of the intrinsic mitochondrial pathway, increased reactive oxygen species (ROS) production, leading to redox imbalance, increased the Bax to Bcl-2 ratio, cytochrome c release, caspase activation, PARP-1 activation, and AIF translocation to the nucleus [3].

In conclusion, MsrB3 plays a crucial role in maintaining cell survival, especially in cancer cells, mainly through modulating the intrinsic apoptosis pathway and ER stress status. The findings from gene knockout-like models in cancer research have revealed its significant contribution to understanding cancer cell death mechanisms, which may provide potential therapeutic targets for cancer treatment [1,2,3].