KINE 1000 Lecture Notes - Lecture 5: Ubiquitin, Ubiquitin Ligase, Cdk Inhibitor
4 Jun 2018
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Cell Cycle Cotrol Syste
• Cycle control is like a timer that triggers events of cell cycle in sequence
• Control system is independent to events it controls
• Control system responds to information received back from processes
• If unsuccessful completion of DNA synthesis, signals are sent to control system to delay
progression to M phase
• Time delays for machinery to be repaired & prevent disaster
• Control system is series of biochemical switches, which initiates specific cell-cycle
events
• Increase in accuracy & reliability of cell cycle progression- complete & irreversible
• Control system is adaptable & responds to intracellular or extracellular signals
• Three Major Regulatory Transitions:
o Start (or resistriction point) in late G1 – cell commits to chromosomes duplication
o G2/M transitions- triggers early mitotic event that leads to chromosome alignment
o Metaphase-to-Anaphase transition- stimulates sister-chromatid separation,
• System detects problems inside or outside cell. Example if it detects problems in
completion of DNA replication, it holds cell at G2/M transitions
• If extracellular conditions are not right for cell proliferation, control system blocks
progression through start & preventing division
Cycle System Depends on Activated Cyclin-Dependent Protein Kinases (Cdks)
• Protein kinases called cyclin-dependent kinases (Cdks)
• Activity of kinases rises/ falls throughout cycle- changes in phosphorylation of
intracellular proteins that initate or regulate major events of cell cycle
• Ex: increase in cdk activity at G2/M transitions increase phosphorylation of proteins that
control chromosome condensation, nuclear-envelope breakdown & spindle assembly
• Cdks depend on cyclins to have kinase activity
• Cyclins undergo cycle of synthesis & degradation; levels of cdk proteins are constant
• Cyclic changes in cyclin proteins regulate assembly & activation of cyclin-cdk complexes
• 4 Classes of Cyclins – defined by stages of cell cycle:
1. G1/S-cyclins- activate Cdks in late G1. Trigger progression through start, resulting
to cell-cycle entry. Levels fall in S-phase
2. S-cyclin bind cdks after progression through start & stimulate late chromosomes
duplication. Remain elevated until mitosis.
3. M-cyclins- activate cdks that stimulate entry into mitosis at G2/M transition. M-
cyclins fall in mid-mitosis
4. G1-cyclins – activate G1/S cyclins
• Cyclin proteins activate cdk & directions it to specific target proteins
• Cyclin-cdk complex phosphorylates different substrate protein
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