Wsb1, short for WD repeat and suppressor of cytokine signaling box containing 1, is an E3 ubiquitin ligase. Its major expressed isoform is a substrate recognition protein within an E3 ubiquitin ligase, capable of binding diverse targets and mediating ubiquitinylation and proteolytic degradation. Wsb1 is involved in multiple pathways, such as β -catenin signaling, NF -κB pathway, and is associated with processes like hypoxia response, glucose metabolism, immune regulation, and thyroid hormone homeostasis. It has significance in developmental biology and is closely related to cancer and other diseases [2].

In cancer research, in 10 cancer cell lines and clinical samples, Wsb1 has a highly positive correlation with c -Myc. It is a direct target gene of c -Myc and can positively regulate c -Myc expression through the β -catenin pathway, forming a feedforward circuit promoting cancer development. In the Bel -7402 xenograft model, overexpressing Wsb1 strengthened the tumor-driven effect of c -Myc overexpression [1]. In prostate cancer, increased Wsb1 expression was associated with higher grades and worse prognosis, and MDS showed its central role in influencing other key genes involved in PC progression [3]. Wsb1 also promotes tumor metastasis by inducing pVHL degradation, and overcomes oncogene-induced senescence by targeting ATM for degradation [6,7].

In idiopathic pulmonary fibrosis, conditional deletion of Wsb1 in adult mice ameliorated bleomycin-induced pulmonary fibrosis, with Wsb1-deficient mice showing reduced lipofibroblast to myofibroblast transition but enhanced alveolar type 2 proliferation and differentiation [4]. In myocardial ischemia-reperfusion injury, overexpression of Wsb1 relieved the injury by activating β -catenin signaling via promoting GSK3β ubiquitination [5].

In conclusion, Wsb1 is an important E3 ubiquitin ligase involved in multiple biological processes and pathways. Studies using gene knockout or conditional knockout mouse models have revealed its significant roles in cancer development, metastasis, pulmonary fibrosis, and myocardial ischemia-reperfusion injury. These findings provide potential therapeutic targets for related diseases.