Wbp2-flox Mouse

WBP2, also known as WW domain-binding protein 2, is an oncogenic transcriptional co-factor. It interacts with multiple key signaling pathways such as ER/PR, EGFR, PI3K, Hippo, and Wnt in cancer [3]. In the Hippo pathway, it associates with transcriptional co-activators YAP and TAZ, and also modulates upstream Hippo components like LATS2 and WWC3 [2]. Additionally, it has a role in miRNA biogenesis by interacting with the microprocessor complex [4].

In cisplatin-induced acute kidney injury (CP-AKI), WBP2, highly expressed in renal proximal tubular cells, was found to be downregulated. Mechanistically, WBP2 interacted with GPX4 via its PPXY1 motif, competing with HSC70 for binding to GPX4's KEFRQ-like motifs, thus inhibiting chaperon-mediated autophagy of GPX4 and decelerating ferroptosis to alleviate CP-AKI [1]. In triple-negative breast cancer (TNBC), WBP2 enhanced cell migration and invasion under TNF-α stimulation. It potentiated TNF-α-induced NF-κB transcriptional activity and nuclear localization by promoting ubiquitin-mediated proteasomal degradation of NFKBIA. WBP2 also induced mRNA stability of BTRC, which targets NFKBIA for ubiquitination and degradation [5].

In conclusion, WBP2 is involved in multiple crucial biological processes and disease conditions. In CP-AKI, it plays a protective role by inhibiting ferroptosis. In breast cancer, especially TNBC, it promotes cancer cell aggressiveness through modulating specific signaling pathways. These findings from functional studies, such as those in relevant disease models, enhance our understanding of WBP2's functions and provide potential therapeutic targets for related diseases.