Cyclic exposure to hypoxia and reoxygenation selects for tumor cells Biology Diagrams The cell cycle is an important cellular process whereby the cell attempts to replicate its genome in an error-free manner. As such, mechanisms must exist for the cell cycle to respond to stress signals such as those elicited by hypoxia or reduced oxygen availability. This review focuses on the role of transcriptional and post-transcriptional mechanisms initiated in hypoxia that interface with
HIFs bind to hypoxia response elements (HREs) in the promoter regions of a large number of targets, including those involved in cell survival, angiogenesis, glycolysis, and invasion/metastasis. Certain mutations in TSC2 confer a growth advantage to cells by repressing hypoxic mTORC1 inhibition and hypoxia-induced cell cycle arrest 135. The hypoxia response mounted by the HIFs promotes cell survival and energy conservation. As such, this response has to deal with important cellular process such as cell division. In this review, the integration of oxygen sensing with the cell cycle will be discussed.
Role of Hypoxia in the Control of the Cell Cycle Biology Diagrams
Mechanisms of cell cycle control in response to hypoxia Cells placed in severe hypoxia undergo a rapid cessation of cell cycle progression and DNA synthesis. The arrest is complex, and has components in multiple phases of the cell cycle, with G1/S, S phase and G2/M arrests all being reported in the literature [87] .
In addition, we discuss how the cell cycle can alter the hypoxia response. Overall, the cellular response to hypoxia and the cell cycle are linked through a variety of mechanisms, allowing cells to respond to hypoxia in a manner that ensures survival and minimal errors throughout cell division. Keywords: hypoxia, cell cycle, HIF, PHDs, 2-OGDs Cyclin D1, a downstream target of p38 , has been implicated in regulating progression through the G 1 phase of the cell cycle (45, 46). In PC12 cells, hypoxia causes a decrease in cyclin D1 protein levels and also causes cells to accumulate at the boundary between the G 0 and G 1 phases of the cell cycle . Both of these effects are partially
Role of Hypoxia in the Control of the Cell Cycle Biology Diagrams
The transcriptional response to hypoxia and the role of hypoxia inducible factors have been extensively studied. Yet, hypoxic cells also adapt to hypoxia by modulating protein synthesis
