Using this method, we screened for small-molecule modulators of SMAD ubiquitin regulatory factor 1 (SMURF1), which belongs to the NEDD4 family of E3 ubiquitin ligases and is an attractive therapeutic target because of its roles in tumorigenesis.
Smad ubiquitylation regulatory factor 1 (Smurf1) has been identified to play a critical role in bone homeostasis, development, cell cycle regulation and tumorigenesis.
Together with its closely related homolog Smurf1, Smurf2 was initially recognized as a negative regulator of transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling, but subsequent studies have expanded its function to regulate many different signaling pathways and play important roles in genomic stability, cell polarity, tissue homeostasis and carcinogenesis.
The HECT-type ubiquitin ligase Smurf1 (Smad ubiquitination regulatory factor-1) plays the prominent role in regulation of bone formation, embryonic development, and tumorigenesis by directing the ubiquitin-proteasomal degradation of specific targets.
Thus, we propose that the PKA-Smurf1-PIPKIγ pathway has an important role in pulmonary tumorigenesis and imposes substantial clinical impact on development of novel diagnostic markers and therapeutic targets for lung cancer treatment.