The dysregulation of the cell cycle in oncogenesis

• The cell cycle is a series of tightly integrated and regulated events that allow the cell to grow and undergo mitosis¹³
  • Under normal circumstances, damage to the cell causes the cell cycle machinery to stop to enable cellular repair before division takes place
  • If the cell is not reparable, apoptosis is induced
  • When disruption occurs in normal checkpoints in the cell cycle, oncogenesis can occur
• Proteins called cyclin-dependent kinases (CDKs) play an essential role in cell cycle control¹³
  • When CDKs are bound by proteins known as cyclins, which have a regulatory function, the cell cycle is driven forward
  • The inhibition of these CDK/cyclin complexes is also an important component of cell cycle regulation
  • There are at least 9 CDKs, but not all of them have been clearly characterized. Many cyclins have also been identified
  • CDKs and cyclins are expressed in a temporal-specific manner so that each CDK and cyclin regulates the cell cycle at a specific phase
• When the normal cell cycle is disrupted, cancer can occur. Mantle cell lymphoma (MCL) is an example of such an occurrence (Figure 5)¹⁴
  • The genetic hallmark of MCL is chromosomal translocation t(11;14)(q13;q32), which results in the overexpression of cyclin D1, a protein important for the early control of the cell cycle
• Targeting aberrant activities of proteins involved in the progression of the cell cycle is a current strategy under pursuit in the development of anticancer therapy¹⁴

Figure 5. In mantle cell lymphoma, the expression of cyclin D1 is placed under the control of the IgH promoter. As a result of chromosomal translocation, the upregulation of cyclin D1 is induced. Cyclin D1 bound to CDK4 activates the transcription factor called E2F, releasing it from negative regulation by the tumor suppressor Rb. E2F then helps drive the cell cycle through the G1-S phase of the cell cycle.¹⁴

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