Mitosis: Cell Cycle Inhibitors

By Levi Clancy for Student Reader on
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HumanYeastInhibitsOverview
Wee1 KinaseCyclin-CDKsInhibitory phosphorylation of CDK1 and CDK2. (link
INK4Mid-G1 CDKsINK4s include cyclin-dependent kinase 4 and 6, which have important tumor suppression activity by inhibiting the mid G1 CDKs, thus inhibiting passage through G1. Both genes encoding INK4a are mutated in many human tumors, lessening their ability to block passage into G1.
p21, p27, and p57Sic1S-Phase Cyclin CDKsBinds and inhibits S-phase cyclin-CDKs (p21, p27, and p57 inhibit Cyclin E-CDK2). Activated by G1 cyclin-CDK (CDK=Cdc28 in budding yeast). Yeast Sic1 is phosphorylated by G1 cyclin-CDKs, and must be phosphorylated at at least six sites by G1 cyclin-CDKs before it is bound sufficiently well by SCF to be polyubiquitinated. Each of these sites are relatively poor substrates for the G1 cyclin-CDKs. Sic1 must be phosphorylated by G1 cyclin-CDKs at at least six sites by G1 cyclin-CDKs before it is bound sufficiently well by SCF to be polyubiquitinated. Each of these sites are relatively poor substrates for the G1 cyclin-CDKs.
Mad2Mad2AnaphaseMad1 binds to the kinetochore. When Mad2 binds to that then it is activated. (One unattached kinetochore is sufficient to inhibit all Cdc20 in the cell.) But when microtubules attach, the tension at the kinetochore leads to Mad2 degradation. If the sister chromatids do not attach to opposite poles, the spindle checkpoint is triggered. Mad2, which is normally bound to Mad1 in a Mad1/Mad2 complex then binds to the anaphase-promoting complex (APC) to form an APC/Mad2 complex. Binding to the APC prevents the formation of the APC/Cdc20p complex which is necessary to begin anaphase. The binding of Mad2 proteins to the APC effectively prevents the cell from transitioning into the anaphase until all of the chromatids are properly attached to opposite spindle pole bodies.
RbSee below.
Sic1S-phase cyclin-CDKs
Cdc14 PhosphataseWhen MPF acts during the transition form prophase to anaphase, Cdc14 phosphatase reverse these effects during late anaphase, telophase and interphase.
SecurinAn inhibitor related to anaphase triggering.
Chk1/Chk2 kinasesCdc25C/Cdc25aCheckpoint controls, inactivate Cdc25C and Cdc25a phosphatases to induce cell-cycle arrest.