Oncogenes and Cell Cycle (Herschman)

Question 1

What makes v-erbB a dominant oncogene?

Answer 1

It is only the C terminus of the EGF receptor so has no growth factor binding domain and is thus constitutively active

Question 2

What makes PDGF a dominant oncogene?

Answer 2

If a cell is infected with an RNA tumor virus, PDGF is expressed INSIDE the cell and this autocrine signaling can lead to cancer

Question 3

What makes v-fos and v-jun dominant oncogenes?

Answer 3

If cell is infected with RNA tumor virus, the transcription factors v-fos and v-jun are expressed and transcribe genes that can lead to cancer

Question 4

Are there dominant oncogenes in the Ras pathway?

Answer 4

Yes: ligand itself, receptor, Ras, Raf, transcription factors

Question 5

Normal pathway leading to Ras signaling

Answer 5

Growth factor ligand binds to receptor → receptor is phosphorylated → now Grb2, which is attached to GNEF via SH3 domains, recognizes and binds phosphorylated receptors → Ras binds GNEF → binding causes Ras to release GDP and take up GTP → Ras-GTP is now active and can signal → GAP binds Ras to help it cleave GTP to GDP and Ras is now inactive

Question 6

What does active Ras (Ras-GTP) do?

Answer 6

Activates a protein kinase cascade:

Ras → RAF → MAPKK → MAPK → nucleus to phosphorylate transcription factors, making them active

Question 7

What is the difference between viral Ras and cellular Ras?

Answer 7

Viral Ras cannot interact with GAP, so it is locked in the “ON” position

Question 8

Can single point mutations in genes contribute to cancer?

Answer 8

Yes

1) Ras unable to bind GAP
2) G alpha subunit leads to endocrine tumors
3) bRaf mutation in 2/3 of melanoma tumors (furthermore, 50% of patients have exact same mutation)

Question 9

Is Ras mutated in many human cancers?

Answer 9

Yes, 1/3 of human cancers have Ras mutation

Question 10

Diagram all the steps of the Ras pathway. From initation to gene expression.

Answer 10