Smurf2 Suppresses Proliferation and Cell Cycle of Triple-Negative Breast Cancer Cells by Promoting the Polyubiquitination and Degradation of RPL35A

Human L35a ribosomal protein (RPL35A) has been reported to confer higher drug resistance and viability to triple-negative breast cancer (TNBC) cells, but the mechanism related to its promotion of TNBC malignant progression is still unclear. Here, we found that silencing of RPL35A could inhibit the proliferation of TNBC cells by suppressing the G1/S phase transition. Furthermore, SMAD-specific E3 ubiquitin protein ligase 2 (Smurf2) was found to be a potential upstream ubiquitin ligase of RPL35A. Smurf2 could interact with RPL35A and promote its degradation and K63-linked polyubiquitination, thereby suppressing the G1/S phase transition and proliferation of TNBC cells. In addition, the roles of Smurf2 were confirmed in a xenograft mouse model. Finally, we found a negative correlation between the protein levels of RPL35A and Smurf2 in human TNBC tissues. In summary, Smurf2 inhibits the proliferation of TNBC cells by blocking the cell cycle process, which is associated with regulating RPL35A.