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Control of the Cell Cycle
Ch. 12
Section 12.3
The Main Idea
• The Cell Cycle is regulated by a molecular control system
How often do cells divide?• Different types of cells divide at different
times– Skin cells divide frequently – Liver cells divide infrequently– Mature nerve and muscle cells do not divide at all
• These differences are the result of regulation of these cells at the molecular level
What drives the cell cycle?
• Very specific chemical signals in the cytoplasm control the cell cycle
• This hypothesis was tested by fusing the nuclei of 2 cells– Each cell was in a
different phase of the cell cycle
E.g. one cell in G1, while the other was in mitosis
The G1 cell would immediately enter mitosis– Seems to support the idea
that chemicals in the cytoplasm of the cell in mitosis caused the G1 cell to also go into mitosis
The Checkpoints
• The signals in the cycle are transmitted via signal transduction pathways
Quick Think
What controls the cell cycle?
The CELL CYCLE CONTROL SYSTEM
• A set of molecules that operate in a cycle to trigger and coordinate the events of the cell cycle
The CELL CYCLE CONTROL SYSTEM
• A good analogy is the timing device on a washing machine– Each step happens on it’s own– Driven by an internal clock that tells it when to begin
each new step– Regulated by both internal signals (tub is full of
water) and external signals (pushing the start button)
CHECKPOINTS in the Cell Cycle Control System
• A critical control point in the cell cycle where the cycle stops until a go-ahead signal is received
The checkpoints
• The G1 checkpoint seems to be an especially important one– If the go-ahead signal is
received here, the cell usually completes S, G2, and M phase
– If not signal is received, the cell goes into G0, a non-dividing state
There are 3 major checkpoints
• G1 checkpoint
• G2 checkpoint
• M checkpoint
Quick Think
How do checkpoints help regulate the cell
cycle?
The “chemicals” that control the cell cycle
• 2 types of proteins:– Cyclins– Cyclin-dependent
kinases (Cdks)• Remember a kinase is a
protein that phosphorylates other molecules
• These kinases are only active when attached to a cyclin protein
The “chemicals” that control the cell cycle
• Cyclin levels rise a lot during interphase
• Cyclin levels fall quickly during mitosis
The “chemicals” that control the cell cycle
• Peaks in the activity of cyclin correspond to peaks in the activity of MPF– M-phase promoting factor– This protein bonds to cyclin & triggers the
passage of the cell from the G2 checkpoint into mitosis
MPF• Triggers other
protein kinases• Stimulates the
breakdown of the nuclear membrane
• Triggers the breakdown of cyclin
Examples of other cell cycle regulators
1. A signal in the M phase checkpoint ensures that all the chromosomes are properly attached to the spindle fiber
1. Helps ensure that there are no missing or extra chromosomes in the new cells
2. Another signal delays anaphase until all the until all the spindles are attached to the centrosomes
1. Once attached, another signal causes the proteins holding the sister chromatids together to break down
Quick Think
How do cyclins and MPF help regulate the
cell cycle?
Cancer• Cancer cells do not
respond normally to the control mechanisms
• These cells divide excessively and invade other tissues
Cancer• Cells turn cancerous when a
single cell undergoes a transformation (the process that converts a normal cell to a cancer cell)
• Normally, the immune system finds and destroys transformed cells
• Cells that are not destroyed may divide excessively and form a tumor - a mass of abnormal cells
Cancer cell (gray) being attacked by immune system cells (green)
Cancer
• A tumor that stays at the original site forms a lump called a benign tumor
• These usually do not cause problems and can be removed surgically
Ready?…
Benign Tumors…Before & After
Benign Tumors…Before & After
Cancer
• Malignant tumors - the cells become invasive enough in other tissues to impair the functions of organs
Cancer• Cancerous cells also
become “loose” (lose their attachment to other cells) and are carried into other tissues in the blood stream, where they start new tumors
• This is called metastasis
Cancer• Cancer cells are
abnormal in that:– Odd number of
chromosomes– Disabled metabolism– Nonfunctioning
metabolism– Secrete signal molecules
that cause blood vessels to grow toward a tumor
Treatments for Cancer• High energy radiation• Chemotherapy
– Drugs that interfere with the cell cycle
• Taxol prevents cells from moving past metaphase
• Many side effects due to the effect on normal cells
• These treatments target cells that are dividing rapidly
Causes of Cancer
• There are many
• All causes involve the alteration of genes that help control the cell cycle