Question

List three different types of retrovirus-encoded oncogenes that are represented by proto-oncogenes in normal cells. Briefly describe the general function of the viral oncogene or its corresponding proto-oncogene.

Answer 1

Retroviruses are the original source of oncogenes. there are morethan 30 retroviral oncogenes identified exclusively in rodent and avian viruses. some of the retrovirus encoded oncogenes are src, myc, ras, erbB etc. Discovery of such oncogenes consolidated the view of cancer as a genetic disease.

Src

• first retroviral oncogene discovered
• oncogene of Rous sarcoma virus (RSV)
• src protein function- tyrosine kinase activity
• in 1980 the cellular and viral src genes were sequenced
• viral src differs from cellular src in a C-terminal deletion, which keeps the viral src constitutively active. so that cellular src has lower kinase and negligible oncogenic activity than viral src

Myc

• emerged after src
• oncogene of Myelocytomatosis virus
• the cellular homolog of retroviral myc gene is c-MYC
• c-Myc act as a transcriptional regulator, but it alone fails to bind DNA under physiological conditions.
• c-Myc oncogene encodes a helix-loop-helix leucine zipper transcription factor that dimerises with its partner protein Max, to transactivate gene expression (which means cMyc-Max dimer can bind to DNA and act as a transcriptional regulator)
• the c-Myc- Max heterodimer also repress gene expression via binding to the transcription factor Miz1.

Ras

• two pricipal viruses carry this oncogene namely Harvey sarcoma virus and Kirsten sarcoma virus
• Ras has guanine nucleotide binding activity. Ras is a GTPase and in its active form it binds to GTP with the help of an enhancer called EGFR. A guanine nucleotide exchange factor (GEF) stimulates the release of GDP from ras and enhances loading with GTP.
• the GTPase activity of ras is stimulated by association with a GTPase activating protein (GAP).
• activated ras also binds to catalytic subunit of PI3K , an important step for PI3K signaling.