WW domain-containing oxidoreductase (WWOX) phosphorylated at Serine 14 (pS14-WWOX)

WW domain-containing oxidoreductase (WWOX) is a multi-functional protein that acts as a tumor suppressor and a key regulator of neurodegeneration (UniProt Q9NZC7). Its biological activity is highly regulated by site-specific phosphorylation: while phosphorylation at Tyr33 (pY33-WWOX) is pro-apoptotic and anti-cancer, phosphorylation at Serine 14 (pS14-WWOX) is associated with disease progression, including cancer growth and Alzheimer's disease (AD). pS14-WWOX and its associated signaling complexes, such as the IκBα/WWOX/ERK complex, accumulate in cancerous lesions and the brains of AD patients, where they promote cell survival, migration, and protein aggregation. Therapeutic strategies focus on suppressing Ser14 phosphorylation or disrupting pS14-WWOX-dependent complexes using peptides like Zfra or specific antibodies. For instance, the Zfra peptide has been shown to reduce pS14-WWOX expression, thereby inhibiting tumor metastasis and mitigating neurodegeneration in animal models. Modulating the pS14-WWOX signaling axis represents a novel approach for treating malignancies and neurodegenerative disorders by shifting the protein's activity from a pro-survival to a pro-apoptotic state.

Other names

Phospho-Ser14-WWOXpS14-WOX1pS14-FORWWOX-dependent signaling complexesIκBα/WWOX/ERK complexpS14-WWOX signaling complexes

Inhibition of Ser14 phosphorylation of WWOX or modulation of WWOX-dependent signaling complexes to suppress disease progression and promote pro-apoptotic signaling.