cular and Cellular Pathobiology R RB - E 2 F 1 Pathway Regulates Autophagy

Downloa ophagy is a protective mechanism that renders cells viable in stressful conditions. Emerging evidence ts that this cellular process is also a tumor suppressor pathway. Previous studies showed that cyclindent kinase inhibitors (CDKI) induce autophagy. Whether retinoblastoma protein (RB), a key tumor ssor and downstream target of CDKIs, induces autophagy is not clear. Here, we show that RB triggers agy and that the RB activators p16INK4a and p27/kip1 induce autophagy in an RB-dependent manB binding to E2 transcription factor (E2F) is required for autophagy induction and E2F1 antagonizes uced autophagy, leading to apoptosis. Downregulation of E2F1 in cells results in high levels of agy. Our findings indicate that RB induces autophagy by repressing E2F1 activity. We speculate that autoph this newly discovered aspect of RB function is relevant to cancer development and therapy. Cancer Res; 70(20); 7882–93. ©2010 AACR.