Mitosis and Cancer

Question 1

How does Ras protein gain a gain-of-function mutation?

Answer 1

Ras gene codes for a G-protein that is found on cell membranes.
G proteins are coupled to certain membrane
receptors and play important roles in cell signaling pathways.
Under normal conditions, binding of an appropriate growth factor to a receptor will trigger activation of ras protein. A GTP molecule will displace the GDP in the ras protein.
Active ras protein passes on signal to series of cytoplasmic kinases, activating
transcription factors –> turn on genes for proteins that stimulate cell cycle.
* To turn the pathway off, ras protein hydrolyses its bound GTP to GDP, and becomes inactive again.
A point mutation in the ras oncogene may cause a change in 3D conformation of the ras protein.
* The altered ras protein loses its ability to hydrolyse GTP to GDP.
* As a result, the altered ras protein is constitutively active (becomes a hyperactive ras protein). Thus,
it will continuously deliver signals for cell growth and division, resulting in uncontrolled cell division.

Question 2

What are the ways that oncogenes can gain a gain-of-function mutation?

Answer 2

• Point mutation
• Chromosomal rearrangement
• Gene amplification
• Insertional mutagenesis