Biochemistry II: Signals, Proliferation, Genes, and Sports

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Phosphorylation and proteolytic regulation of cell cycle function

Phosphorylation and proteolytic regulation of cell cycle function (Figure 1)
MAP kinase phosphorylation in the RAS-RAF pathway responsible for cell cycle initiation is essential (see Cyclin D synthesis)

  • Phosphorylation is an extremely important regulatory mechanism for cyclin-dependent kinases that determine cell cycle function
  • In order for a CDK to be fully activated, it requires phosphorylation on the threonine residues, which is accomplished by the CAK enzyme.
  • At the same time, the activity of cyclin-CDK complexes is inhibited by phosphorylation: THR, TYR side chains near the N-terminus, their dephosphorylation is performed by cdc25 phosphatase.
  • Proteolysis regulates CDK activity by breaking down CDK-activating cyclins or inhibitors CKI, that inhibit CDK, thereby initiating the transition from metaphase to anaphase.
  • It is irreversible, so it gives decisive direction to certain processes.
  • Examples: Proteolysis that requires CDC34 helps to initiate DNA replication by inhibitor degradation, similar to that of mitotic CDK1.
  • In anaphase, proteolysis helps to exit mitosis by breaking down mitotic cyclins and anaphase inhibitors.
  • An important part of phosphorylation regulation is the relationship between the retinoblastoma protein and E2F.

 

Illustration of the Retinoblastoma protein in the cell-division cycle

Figure 1. The cell cycle representation (with permission from CISBIO)

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