AP Biology · Lesson 3

Cyclins, growth signals and cancer

Know Know it

Inside the cell, the cycle is driven by cyclins and cyclin-dependent kinases (CDKs). A CDK is a kinase that is active only when a cyclin is bound to it. The amount of CDK stays fairly steady, but cyclin levels rise and fall: a cyclin builds up, binds its CDK, and the active pair phosphorylates target proteins that move the cell past a checkpoint. Then the cyclin is broken down and the CDK goes quiet. A CDK paired with a mitotic cyclin drives the cell from G2 into mitosis. That cyclin is broken down around the start of anaphase, which lets the cell finish mitosis and leave M phase.

Signals from outside matter too. Growth factors are signal proteins that tell cells to divide; at a wound, for example, platelets release a growth factor that makes nearby connective tissue cells divide. A growth factor binds a receptor, often a receptor tyrosine kinase, and the pathway inside switches on genes, including cyclin genes, that move the cell past the G1 checkpoint. Normal cells in a dish also stop dividing when they crowd into a single layer (density-dependent inhibition) and divide only when attached to a surface (anchorage dependence).

Cancer is cell division that no longer stops, caused by mutations in the genes that control the cycle. Proto-oncogenes code for proteins that promote division, such as growth factor receptors and relay proteins. A mutation that makes such a protein overactive, or makes too much of it, turns the gene into an oncogene: the go signal stays on. Tumor suppressor genes code for proteins that stop or pause division or trigger apoptosis. A mutation that disables one removes a brake. The best known, p53, codes for a transcription factor that responds to DNA damage by stopping the cycle in G1 so the DNA can be repaired, or by triggering apoptosis if the damage is too great.

A cell usually needs several mutations, often in both kinds of genes, before it becomes a cancer cell. Cancer cells keep dividing without growth factors, ignore crowding and checkpoints, and often avoid apoptosis. Apoptosis itself is programmed cell death: the cell breaks down its own contents in an orderly way and its neighbors clear the pieces. Besides removing damaged cells, it shapes the body; in a human embryo, the cells between the developing fingers die by apoptosis.

Trap Gas pedal versus brakes

An oncogene is a gain of function: one overactive copy can be enough, like a gas pedal stuck down. A tumor suppressor gene usually causes trouble only when both copies are disabled, like losing both brakes. So a person who inherits one disabled copy of a tumor suppressor gene does not have cancer, but each cell is one mutation away from losing that brake.

Worked example Easy

What does a cyclin-dependent kinase need in order to be active?

  1. A cyclin bound to itAnswer
  2. To be released from its cyclin
  3. A growth factor bound to it outside the cell
  4. To be broken down after anaphase

How to solve it

  1. The name gives the rule: cyclin-dependent kinase.
  2. CDK levels stay fairly steady; cyclin levels rise and fall.
  3. The CDK is active only when a cyclin is bound to it.

Why each choice is right or wrong

  • A. Correct. As its name says, a CDK depends on a cyclin: it is active only while a cyclin is bound to it.
  • B. Incorrect. Losing its cyclin turns a CDK off, which is why breaking down the cyclin ends the CDK's activity.
  • C. Incorrect. Growth factors bind receptors on the cell surface, not CDKs, which work inside the cell.
  • D. Incorrect. It is the cyclin, not the CDK, that is broken down around the start of anaphase, and a broken-down protein cannot be active.

Explain Explain it

Task verbs: explain, predict

To explain a cell-cycle control result, name the protein or signal that normally says go or stop, then say what the change did to it. An overactive go signal (an oncogene) and a missing stop signal (a disabled tumor suppressor) both lead to the same result: division that does not stop when it should. For a prediction, give the direction first, then that chain.

Worked example Medium

A mutation leaves a relay protein in a cell's growth factor pathway stuck in its active form. What kind of gene carries this mutation, and what is its effect on the cell?

  1. A tumor suppressor gene; the cell divides with no growth factor present
  2. An oncogene; the cell stops dividing even when growth factor is present
  3. An oncogene; the cell divides with no growth factor presentAnswer
  4. A tumor suppressor gene; the cell dies by apoptosis

How to solve it

  1. The relay protein carries a go signal from the growth factor receptor.
  2. A gene for a go protein is a proto-oncogene; an overactive form is an oncogene.
  3. Stuck on, the relay protein signals even with no growth factor, so the cell divides when it should not.

Why each choice is right or wrong

  • A. Incorrect. A relay protein that promotes division comes from a proto-oncogene; a tumor suppressor's protein stops division instead.
  • B. Incorrect. A stuck-on relay protein sends the go signal all the time, so the cell keeps dividing rather than stopping.
  • C. Correct. The gene for a relay protein that promotes division is a proto-oncogene; stuck on, it is an oncogene that signals divide with no growth factor.
  • D. Incorrect. The relay protein promotes division, so its gene is a proto-oncogene, and a stuck-on go signal drives division, not cell death.

Predict Your turn

In a fictional cell line, both copies of the p53 gene carry a mutation that leaves the p53 protein unable to work. The cells are exposed to a chemical that damages DNA. Predict whether the cells will keep dividing. Then explain the normal job of p53 when DNA is damaged, and explain what the loss of p53 means for the DNA of the daughter cells.

Write it, then compare. Nothing you type here is saved or graded.

Compare with a model answer

A full answer does this

  • Predicts that the cells keep dividing despite the DNA damage
  • Explains that p53 normally stops the cycle when DNA is damaged, so it can be repaired, or triggers apoptosis if the damage is too great
  • Explains that damaged DNA is then copied and passed on, so daughter cells inherit mutations

Model answer

The cells will keep dividing even though their DNA is damaged. Normally, p53 responds to DNA damage by stopping the cell cycle at the G1 checkpoint so the DNA can be repaired, and if the damage is too great it triggers apoptosis. Without working p53, nothing stops these cells, so they copy the damaged DNA and divide, and the daughter cells inherit the damage as mutations. Over many divisions, more mutations build up, which raises the chance that a cell becomes a cancer cell.

Apply Apply it

Practice these topics. AP Practice questions on exactly what this lesson covers, with an explanation for every answer.

Practice these topics