Selenium-binding protein 1 suppresses cell cycle progression via cyclin-dependent kinase 2 breakdown in colon carcinoma.

Selenium-binding protein 1 (SELENBP1) may act as a tumor suppressor gene in colorectal cancer (CRC). However, it remains unclear whether SELENBP1 regulates cell cycle progression governed by cyclin-dependent kinase 2 (CDK2). Herein, we validated the intracellular binding of SELENBP1 to CDK2, based on our previous observations. We investigated the regulatory effects of SELENBP1 on retinoblastoma protein (RB) signaling pathway activation and CDK2-mediated cell cycle progression. Finally, we explored the molecular mechanism through which SELENBP1 inhibited CDK2 expression. Both ectopically induced and endogenously expressed SELENBP1 bound to CDK2 in cultured CRC cells. SELENBP1 inhibited the expression of CDK2 and activated RB signaling. Studies have indicated that SELENBP1 inhibits the cell cycle and suppresses tumor growth. Mechanistic studies showed that SELENBP1 might suppress cancer cell growth by causing CDK2 breakdown via ubiquitination. We conclude that SELENBP1 plays a distinct role as a potential tumor suppressor-associated gene that blocks the interphase and mitosis continuum and suppresses tumor growth in CRC by inducing the ubiquitination-mediated degradation of CDK2.