Course1, Test1, Ras Oncogene

Front 1

Thinks about the basic characteristics of Ras oncogene and what is does:

Back 1

The Ras oncogene is a GTPase that has a slower rate of GTP hydrolysis in the mutant variant. This is because the enzyme GAP (which helps hydrolyzes GTP [activated] Ras to GDP [inactive] Ras) is unable to stimulate the hydrolysis of the Ras-GTP bond. As a result Ras binds to cell surface and initiates a phosphorylation cascade that causes uncontrollable cell growth.

Front 2

Growth activator (dominant oncogene) is generally defined (according to his slide) as:

Back 2

When a mutated cell and normal cell's chromosome mix, they share two different alleles for the same gene. When the mutated allele is expressed (dominant), the phenotypical characteristics are tumorigenic growth responses.

Front 3

Growth Suppressor (recessive oncogene) is generally defined (according to his slide) as:

Back 3

When a mutated cell and normal cell's chromosome mix, they share two different alleles for the same gene. When the normal allele is expressed, the phenotypical characteristics are: no tumor cells. So the oncogene is recessive, and the beneficial allele is considered a Growth Suppressor.

An example of this is NF1. When the allele for NF1 is dominant, even in a person with the Ras gene mutation, the tumorigenic growth factors will be suppressed.

Front 4

What is NF1?

Back 4

NF1 is a Ras GAP (the GAP is what inactivates Ras by hydrolyzing GTP). Function: to inhibit cell growth -- to turn off Ras. So the loss of NF1 leads to hyper-activation of Ras. NF1 is a tumor suppressor gene.

The gene for NF1 can be heterozygous: meaning one mutant and one normal. This would lead to loss of some function.

Loss of heterozygosity (LOH) means that you now have two mutant alleles for the gene, which can lead to neurofibromas.

Front 5

What would be the purpose of designing a Farnesyl Transferase inhibitor?

Back 5

There are some posttranslational processes that allow Ras complex to bind to the cell membrane to start the phosphorylation cascade (causing cell growth). Farnesyl (with pyrophosphate [not important] collectively are known as farnysyl-transferase) will allow Ras to bind to the membrane. So if Farnesyl inhibitors are developed for therapeutic purposes, we can inhibit Ras from binding to the membrane.

Front 6

What therapeutic treatments could potentially be designed to stop the phosphorylation cascade (to prevent cell growth) after a Ras oncogene protein has bound to a cells surface?

Back 6

You could design kinase inhibitors which would prevent the cascade effect of the Ras receptor on the cells membrane.

Front 7

How can Farnesyl transferase inhibitors potentially have a positive therapeutic effect for treating Progeria?

Back 7

In people w/o Progeria: Farnesyl binds with Lamin A protein and guides it to the nuclear membrane where Farnesyl then detaches and binds Lamin A. In Progeria, Farnesyl never detaches and it creates an irregular nuclear membrane cell lining. The result is a disease that makes a person have the symptoms grow older quick -- including a very short lifespan. Farnesyl inhibitors can be used to block the addition of Farnesyl to Lamina A for patients with Progeria, so that it can line the membrane properly..