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Normal Cell Function Research Paper

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Normal cell function is to grow, divide, and die; cancer cells on the other hand grow out of control and their main function is to survive and proliferate (55). This uncontrolled growth of cancer cells is due to the alteration of genes. These genes are oncogenes and tumor suppressor genes. Normal genes in the cell are proto-oncogenes that control how often the cell divides. When the proto-oncogene is mutated it becomes an oncogene which results in the gene being permanently turned on or activated. This results in the uncontrolled growth of cells and can lead to cancer. The tumor suppressor gene, in normal functioning cells will slow down cell division, DNA repair mistakes, or tells the cells to undergo apoptosis, but when inactivated it will …show more content…

The PI3K/AKT pathway, when activated, will lead to cell survival, growth and proliferation (18). PI3K phosphorylates phosphatidylinositol triphosphate (PIP3). Once PIP3 is formed a Protein Kinase B (PKB) or AKT molecule is tethered to a pleckstrin homology (PH) domain, which will then lead to the activation of AKT/PKB as a kinase (11). If AKT is activated it can lead to the activation of mammalian target of rapamycin (mTOR) and nuclear factor kappa B (NF-κB) and inhibition of glycogen synthase kinase 3 beta (GSK-3β) and BAD (Figure 2) (13). The activation of mTOR leads to the phosphorylation of p70S6 kinase (p70S6K), which is an activator of translation that turns on cell growth. NF-κB is a transcription factor that, when liberated from IκB, translocates to the nucleus to activate anti-apoptotic and mitogenic genes. When GSK-3β is inactivated, β-catenin is released from the complex resulting in the stimulation of cell proliferation. Phosphorylation of AKT results in the inhibition of BAD and ultimately apoptosis (45). PTEN dephosphorylates PIP3 back to PIP2. It is a negative regulator of PI3K. This dephosphorylation results in the inhibition of AKT signaling pathway. PI3K pathway can be overactive if PTEN faulty …show more content…

In this model, the proteins are characterized into two categories, activators and sensitizers. BIM is an activator that will bind directly to BAX and BAK unless it is sequestered by a pro-survival protein. On the other hand BAD is a sensitizer that displaces the BH3 activators from the pro-survival proteins (17). BH3-only proteins translocate to the mitochondria and bind to other mitochondrial proteins. BAX and BAK are located on the mitochondrial membrane where they undergo conformational changes and oligomerize (24, 30). After this process, BAX and BAK mitochondrial pore formation causes apoptogenic proteins to be released from the mitochondria. BAX-BAK oligomerization can be inhibited by pro-survival proteins like Bcl-2 and Bcl-xL resulting in the inhibition of apoptosis (30, 40, and 44). Pro-survival and pro-apoptotic proteins are competing with each other in order to turn on cell survival or apoptosis, respectively. There are many steps and proteins that are associated with apoptosis. During early apoptosis BIM dissociates from its microtubule complex, translocates to the mitochondria and aids in the release of cytochrome c (33). BIM however, if phosphorylated at serine 69 by ERK, will be targeted for degradation by the proteasome (27). BAD dephosphorylates and inactivates the pro-survival proteins Bcl-2 and Bcl-xL which are bound to BAX on the surface of the

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