Slide 9 of 79
Notes:
Using experimental evidence from the literature, Novak and Tyson filled in the details to form a biochemical model of the cell cycle. In figure A we have what is called the dimer box. There are two phosphorylation sites T and Y, which give us four possible forms. In order to be active T must be phosphorylated and Y must be unphosphorylated. The phosphate is put on and taken off by enzymes and this changes the behavior of the target protein. The T site is phosphorylated very fast by Cak, so most Cdc2/cyclin dimers are in the upper part of the box. Therefore most important regulatory enzymes are Cdc25 and Wee1. Cdc25 is a phosphates that takes the phosphate off the Y site to form active MPF and Wee1 is the kinase that phosphorylates the Y site to form inactivate MPF.
In figure B we see that the activity of Cdc25 and Wee1 are also controlled by phosphorylation. Active MPF phosphorylates both Wee1 turning it off and Cdc25 turning it on. By killing its enemy and helping its friend active MPF creates a positive feedback loop for its own accumulation. This positive feedback loop is a source of instability that generates oscillations.
Figure C shows how the cell gets out of mitosis. The key to exiting mitosis is the regulation of APC. Active MPF indirectly activates APC by phosphorylating IE which then turns on APC. APC degrades cyclin therefore destroying MPF activity at the end of mitosis. A hypothetical IE is introduced because there is clear experimental evidence for a significant time delay between MPF activation and APC activation. IE creates a negative feedback loop with a time delay which can also generate limit cycle oscillations.
