SCIE1106 Lecture Notes - Lecture 26: P53, P21, Restriction Point
Cell Cycle Control
Sunday, 9 October 2016
1:04 pm
Cell Cycle:
• There must be co-ordination in cell division of
o DNA synthesis
o Organelle biosynthesis
o Macromolecule biosynthesis
• Dividing cells must co-ordinate all aspects of their growth
Higher Eukaryotes:
• Cell cycle and proliferation are tightly regulated by integrated controls that continually
evaluate the state of the cell and its environment
• Regulation of somatic cell number is a great example of homeostasis
• Normal cell proliferation is modulated by regulation of the cell cycle - checkpoints
What Controls Passage Through Cell Cycle:
• Small group of heterodimeric protein kinases regulate cell cycle
• This means two different subunits make up the active protein
• And it is an enzyme
• It is a kinase, an enzyme that adds phosphate groups
• Regulatory subunit = cyclins
o Proteins level increase and decrease during cell cycle
• Catalytic subunit = cyclin-dependent protein kinase = Cdk
o Have kinase activity but only when bound by the appropriate cyclin
o The binding of the cyclin not only activates the protein kinase but also
determines what substrate the kinase can phosphorylate
Cell Cycle Control:
• Precise control during development is crucial - determines size and shape of
organs/tissues
• Cell divisions - controlled by complex network of signalling pathways (extracellular
signals and intracellular cues)
• Cell cycle regulatory mechanisms discovered in yeast, worm - also operate in the
somatic cells of higher animals, including humans
• Loss of control/disturbance in the cell cycle = cancer
• Engines that drive CC from one step to the other are the series of protein complexes
called Cdk-cyclins
• Going to the next step in the cycle requires activation of genes whose protein
products are necessary for the next phase
• Variation in Cdk-cyclin activities throughout the cell cycle in mammalian cell
• Widths of bands indicate the relative activities of Cdk-cyclin complexes
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• Cdk's are named 'cyclin depenant' because each Cdk must be attached to a cyclin to
function
• Cyclin tethers target protein so that Cdk can phosphorylate it
• As different cyclins present at different stages of cell cycle, each phase is characterised
by phosphorylation of different target proteins
• Target protein binds to cyclin, part of active Cdk-cyclin complex, placing target
phosphorylation sites close to active sites of Cdk-cyclin complexes
• This activation occurs through the turning on of transcription factors by the Cdk-cyclin
complexes
• The G1, Cdk-cyclin complex activates multiple cellular components
o TFs turn on genes encoding DNA polymerase
o Genes for enzymes to produce deoxyribonucleotides
o Proteins involved in duplication of chromosomes
o Genes for subunits of the next Cdk-cyclin complex
Cell Cycle Regulation:
• Cyclin
o Present only in specific phase of cell cycle
o Unstable, resulting in transient activity
o Appearance of specific cyclin is result of preeding Cdk-cyclin complex - activate
TF for new cyclin
o Also growth factors/mitogens (released locally) induce synthesis of G1 cyclins
• Cyclin-dependent protein kinase (Cdk)
o Substrate specifity and phosphorylation activity controlled by bound cyclin
o Phosphorylate specific target proteins
o Sequential activation of different Cdk-cyclin complexes controls cell cycle
progression
o If an active Cdk-cyclin is present at the wrong time, it will cause inappropriate
gene expression
Cdk Targets:
• How does the phosphorylation of target proteins control the cell cycle?
• Phosphorylation initiates chain of events - including activation of certain transcription
factors
find more resources at oneclass.com
find more resources at oneclass.com
