Protooncogenes

Physiological genes that occur in every cell. Protooncogenes code for proteins that control the growth, division and differentiation of a cell. Thus, many components that influence the growth of a cell can be considered as proto-oncogenes. If a protooncogene mutates (e.g. through the influence of ionising radiation, chemical substances or viruses), this mutation leads to a loss of function of the cell; cell division is no longer promoted; the cell can no longer divide. This leads to programmed cell death (apoptosis) and thus to a physiological selection of the cell. If the protooncogene mutates, however, cell division can also be promoted. This occurs when a growth gene comes under the influence of a promoter that normally has a strong activating effect. In these cases, proto-oncogenes are activated to form oncogenes; the result is uninhibited tumour growth. Normally there is a fine balance between oncogenes and tumour suppressor genes (e.g. p53 tumour suppressor pathway). Currently, more than 100 proto-oncogenes are known.

Proto-oncogenes are divided into several groups according to the proteins they encode:

• Growth factors
• Growth factor receptors
• G proteins (e.g. encoded by the RAS protooncogenes)
• non-receptor protein kinases, e.g. tyrosine kinases, serine/threonine kinases
• nuclear transcription factors e.g. C-Myc protein (see MYC gene below)
• tumor-specific chromosomal aberrations
• Oncogenes from viruses, e.g. tax, the oncogene of HTLV-1, HTLV-2 and the bovine leukosis virus (BLV).

All "cell cycle control genes" are potential proto-oncogenes, as their alteration or dysfunction can mean the loss of control over cell division.