Control of Cell Cycle

How do cells control cell cycle?

How does cancer develop?

The Cell Cycle Control System

• The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock
• The cell cycle control system is regulated by both internal and external controls
• The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received

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Figure 12.15

G₁ checkpoint

G₁

G₂

G₂ checkpoint

M checkpoint

M

S

Control�system

• For many cells, the G₁ checkpoint seems to be the most important
• If a cell receives a go-ahead signal at the G₁ checkpoint, it will usually complete the S, G₂, and M phases and divide
• If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G₀ phase

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Figure 12.16

G₁ checkpoint

G₁

G₁

G₀

(a) Cell receives a go-ahead�signal.

(b) Cell does not receive a�go-ahead signal.

The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

• Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks)
• Cdks activity fluctuates during the cell cycle because it is controlled by cyclins, so named because their concentrations vary with the cell cycle
• MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G₂ checkpoint into the M phase

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Figure 12.17a

(a) Fluctuation of MPF activity and cyclin concentration �during the cell cycle

MPF activity

Cyclin�concentration

Time

M

M

M

S

S

G₁

G₂

G₁

G₂

G₁

Figure 12.17b

(b) Molecular mechanisms that help regulate the cell cycle

Cdk

Degraded�cyclin

Cyclin is�degraded

MPF

G₂�checkpoint

Cdk

Cyclin

M

S

G₁

G₂

Stop and Go Signs: Internal and External Signals at the Checkpoints

• An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase
• Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide
• For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture

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Figure 12.18

A sample of human�connective tissue is�cut up into small�pieces.

Enzymes digest�the extracellular�matrix, resulting in�a suspension of�free fibroblasts.

Cells are transferred to�culture vessels.

Scalpels

Petri�dish

PDGF is added�to half the�vessels.

Without PDGF

With PDGF

10 m

1

2

3

4

• A clear example of external signals is density-dependent inhibition, in which crowded cells stop dividing
• Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide
• Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence

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Figure 12.19

Anchorage dependence

Density-dependent inhibition

Density-dependent inhibition

(a) Normal mammalian cells

(b) Cancer cells

20 m

20 m

Loss of Cell Cycle Controls in Cancer Cells

• Cancer cells do not respond normally to the body’s control mechanisms
• Cancer cells may not need growth factors to grow and divide
• They may make their own growth factor
• They may convey a growth factor’s signal without the presence of the growth factor
• They may have an abnormal cell cycle control system

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• A normal cell is converted to a cancerous cell by a process called transformation
• Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue
• If abnormal cells remain only at the original site, the lump is called a benign tumor
• Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors

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