Abstract: B-cell lymphoma 2 (Bcl-2) has a dual function, acting as both an oncogene and an anti-tumor gene. It is well known that Bcl-2 exerts its tumor promoting function through the mitochondrial pathway. However, the mechanism by which it suppresses tumor formation is not well understood. We have previously shown that Bcl-2 inhibits cell cycle progression from the G₀/G₁ to the S phase after serum starvation, and that quiescent Bcl-2 expressing cells maintain a significantly lower level of mitochondrial reactive oxygen species (ROS) than control cells. Based on the fact that ROS mediate cell cycle progression and are controlled by peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), a key molecule induced by prolonged starvation and involved in mitochondrial metabolism, we hypothesized that PGC-1α might be related to the cell cycle function of Bcl-2. In this paper, we show that PGC-1α is upregulated by Bcl-2 overexpression and downregulated following Bcl-2 knockdown or downregulation after serum starvation. However, Bcl-2 is negatively regulated by PGC-1α expression. Further, co-immunoprecipitation (co-IP) experiments showed that PGC-1α protein is co-precipitated with Bcl-2 at the G₀/G₁ phase. Taken together, our results suggest that PGC-1α interacts with Bcl-2 after serum depletion, and that Bcl-2 might recruit PGC-1α to reduce ROS, which in turn delays cell cycle progression in coordination with Bcl-2.

Key words: B-cell lymphoma 2 (Bcl-2); Peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α); Mitochondria; Reactive oxygen species (ROS); Cell cycle

Please provide your name, email address and a comment

Your Name: Affili: E-Mail Address:

Comment (Please comment in English):


Verification Code(click to change a pic):