Abstract
Rb is a tumor suppressor, and regulates various biological progresses, such as cell proliferation, development, metabolism and cell death. In the current study, we show that Rb knockout in 3T3 cells leads to oxidative redox state and low mitochondrial membrane potential by regulating mitochondrial activity. Our results indicate that Rb plays an important role in controlling redox homeostasis. More importantly, the functions of Rb in modulating cell proliferation, death and transformation are, at least in part, mediated by its controlling cellular redox state. In addition, our results also suggest that the cellular redox state possibly determines various biological activities, including cell survival, death and transformation, where Rb is functioning as a regulator of redox homeostasis.
Highlights
The retinoblastoma protein (Rb) is a well known tumor suppressor, and functions in the control of cell cycle progression and proliferation [1]
Oxidative stress and redox homeostasis are in essence associated with and integrated in metabolism, and thereby, these observations confirm the role of Rb in regulating cellular metabolism
Rb controls redox homeostasis Rb was implicated in the control of redox homeostasis in Drosophila [10]
Summary
The retinoblastoma protein (Rb) is a well known tumor suppressor, and functions in the control of cell cycle progression and proliferation [1]. Rb has been demonstrated to have many other functions, such as preservation of chromosomal stability, induction and maintenance of senescence, regulation of apoptosis, cellular differentiation and angiogenesis [2] All these processes play crucial roles in preventing tumor progression, and probably contribute to Rb tumor suppressor function. The Rb-E2F1 complex can translate signals that sense the metabolic needs of the cell into a transcriptional response and orchestrate a complex control of oxidative and glycolytic metabolisms [4]. Oxidative stress and redox homeostasis are in essence associated with and integrated in metabolism, and thereby, these observations confirm the role of Rb in regulating cellular metabolism
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