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