Regulation of the Cell Cycle

Cell cycle is known, so now we ask what controls it

We have observed many factors that influence a cell’s ability to move forward in the cycle◦ Kinetochores not attached to microtubules◦ Density dependent inhibition◦ Anchorage dependence

Internal and External Factors

Cells anchor to dish surface anddivide (anchorage dependence).

When cells have formed a completesingle layer, they stop dividing(density-dependent inhibition).

If some cells are scraped away, theremaining cells divide to fill the gap andthen stop (density-dependent inhibition).

25 µmNormal mammalian cells

The question becomes, what is happening in the cell

Experiments have shown that proteins are the control molecules

Molecular Control

The Rao Johnson Experiment Experiment 1 Experiment 2

S

S S

G1 G1M

M M

When a cell in the M phase was fused with a cell in G1, the G1 cell immediately beganmitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Something in M phase induced interphase cells to divide.

When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized. S cells contained something that induced regulation in G1

cells.

Conclusion: the S phase proteins work on G1 nuclei, M phase works on everything

Biologists determined it was a complex of two proteins called mitotic promoting factor (MPF) Made of cyclin dependent kinase (CDK) and cyclin

Kinase enzymes turn other proteins on and off by phosphorylating them

inactive cycle protein  ------------->active-P

           ATP ADP

MPF phosphorylates key proteins, inducing mitosis◦ And, activates a protein that destroys cyclin◦ So, it shuts off further division when it has been

activated Similar all three portions of interphase Each is referred to as a “checkpoint” Collectively, they are called growth factors The cell has mechanisms that ensure each

phase is complete before moving onto the next

We have seen this already with the possibility of a cell entering G0

LE 12-15

G1

G1 checkpoint

G1

G0

If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.

Cancer can be thought of as uncontrolled growth of cells◦ They may lack the mechanisms, do not respond

properly to them, or have an error in the pathways

If they stop, it is at a random point

Cancer

Cancer cells do not exhibit anchorage dependenceor density-dependent inhibition.

Cancer cells25 µm

A mass of cancer cells is known as a tumor◦ If this tumor stays in the original site – benign◦ If it spreads to surrounding tissue - malignant

A individual tumor cell can break free from the group and invade other organs◦ It is said to have metastasized◦ Metastasishttp://www.youtube.com/watch?v=rrMq8uA_6iA&feature=related

Unfortunately, these cells can continue to grow if supplied with nutrients◦ Normal cells divide 25-50 before dying

A hexanucleotide sequence TTAGGG Holds DNA together A portion of this is lost every time a cell

divides When it is lost, DNA unwinds, cell death Cancer cells have telomerase

◦ Continually rebuilds the telomeres◦ They are “ageless”

Telomeres

Cancer cell

Bloodvessel

LymphvesselTumor

Glandulartissue

Metastatictumor

A tumor grows from asingle cancer cell.

Cancer cells invadeneighboring tissue.

Cancer cells spreadthrough lymph andblood vessels toother parts of thebody.

A small percentageof cancer cells maysurvive and establisha new tumor in anotherpart of the body.

Cancer

The two most common treatments we have are chemotherapy and radiation treatments

Chemotherapy By definition, treatment of any condition via

chemicals Our focus is on antineoplastic drugs –

cancer fighters Act by targeting rapidly dividing cells

◦ However, this also includes healthy cells such as bone marrow (blood cells) and hair follicles, and sex cells

Treatments

Common side effects – hair loss and a compromised immune system

Essentially theory is the drugs will kill the cancer faster than the patient

If not discovered soon enough, treatment would take too long

Radiation Therapy Beam of subatomic particles that damages

DNA Has to focus on a tumor

With more knowledge on mechanisms of cancer, new treatments are being proposed

Viruses are being designed to specifically target cancer cells

Alternatives