WW domain-containing E3 ubiquitin protein ligase 2 (WWP2)

WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) is an enzyme of the NEDD4 family that mediates the transfer of ubiquitin to specific substrate proteins, targeting them for proteasomal degradation[1][3]. The protein contains an N-terminal C2 domain, four WW domains, and a C-terminal HECT domain, which are crucial for substrate recognition, membrane association, and enzymatic activity, respectively[1]. WWP2 regulates cell proliferation, cell cycle progression, and multiple signaling pathways, including TGF-β/SMAD and PI3K/AKT, largely by ubiquitinating and promoting the degradation of protein targets such as PTEN, SMAD2/3/7, and OCT4[2][3][4][5]. It plays a role in embryogenesis, stem cell pluripotency, and neuronal development, and dysregulation or mutation of WWP2 has been implicated in various cancers, inherited skeletal syndromes, and immune disorders[2][3][5]. WWP2 is considered a potential therapeutic target because of its central role in tumorigenic signaling pathways and regulation of tumor suppressor stability, although no direct drugs against WWP2 are clinically available[3].

Other names

NEDD4-like E3 ubiquitin-protein ligase WWP2atrophin-1-interacting protein 2AIP2WW domain-containing protein 2HECT-type E3 ubiquitin transferase WWP2atrophin-1 interacting protein 2

Potential therapeutic mechanism may involve inhibition of E3 ubiquitin ligase activity to stabilize substrates such as tumor suppressor PTEN or SMAD7[2][5]. Inhibition may disrupt proteasomal degradation of target proteins, thereby intervening in cell cycle regulation or oncogenic signaling[5].