Oncogenic Viruses

Oncogenes are mutated or inappropriately expressed cellular genes that specify proteins in signal transduction pathways. Oncoproteins are the oncogenic gene products that function in signal transduction pathways to transform cells, allowing them to proliferate in an uncontrolled manner, generally resulting in cancerous growths (e.g., malignant tumors in solid tissues).

Viruses such as retroviruses carry oncogenes derived from normal cellular genes (proto-oncogenes) and are called oncoviruses. They also contain viral genes that promote cellular proliferation, thus producing more cells in which mutations in proto-oncogenes might occur. These viruses transform cells when they integrate to become proviruses and disrupt tumor suppressor genes or cause inappropriate expression of normal proto-oncogenes. Transformed cells often proliferate out of control, become immortal, change shape, have new antigenic properties, and lose contact inhibition. Normal cells usually stop proliferating when sufficient contacts have been made with other cells. The loss of contact inhibition allows cells to wander off into other tissues and organs (metastasis) and spread a cancerous growth. In some cases, the oncogenic protein is an overproduced but normal protein, but mostly oncoproteins differ from the normal protein in their amino acid sequence. If the oncoprotein is part of a signal transduction pathway, then the abnormal component stimulates the cell to replicate itself inappropriately. This disruptive transformation may, after several other mutations, yield cancerous cells.

Oncoproteins fit into one of eight categories:
(1) peptide growth factors,
(2) growth factor receptors in the plasma membrane or cytoplasm,
(3) GTP-regulated proteins called G proteins,
(4) membrane receptors with tyrosine kinase or with threonine-serine kinase activities,
(5) cytoplasmic protein kinases with tyrosine kinase activities or with serine-threonine activities,
(6) DNA -binding proteins that function as transcriptional activators or that promote DNA replication,
(7) cyclins that promote the activity of protein kinases, and
(8) proteins that inhibit tumor suppressor proteins.

Almost all of the oncoproteins function in various signal transduction pathways that begin with a signal (peptide or steroid hormone) and end with the activation of transcription and/or the initiation of DNA replication. The oncoproteins override the normal regulation of cells and continuously send signals that activate gene expression and progression through the cell cycle. This increases the chances that mutations will occur in the proto-oncogenes and in tumor suppressor genes (normal cellular genes whose products dampen or inhibit cell replication). The more proto-oncogenes converted into oncogenes, the more unregulated a cell becomes. Similarly, the more tumor suppressor genes that are damaged by mutations, the more signal transduction pathways or cell cycle regulation mechanisms that do not function properly.

Examples of oncogenes:
Ras
Src
Fos
Myb
Abl
Jun