Tumor suppressor genes

Name for a group of recessive genes that code for proteins that control the cell cycle (cell growth). They are also referred to as recessive oncogenes or anti-oncogenes.

Their function reduces the probability that a cell will develop tumors. Genes encoding proteins that induce apoptosis are also classified as tumor suppressor genes. Mutation or deletion of these genes usually leads to loss of function.

This increases the probability of tumor formation.

In this sense, tumor suppressor genes have a comparable effect on mutations as proto-oncogenes (seeoncogenes below). The loss of function only becomes apparent with the loss of both alleles (recessive mutation).

Retinoblastoma gene: A well-known example of a tumor suppressor gene is the retinoblastoma gene localized on chromosome 13. A transforming effect occurs when both alleles are destroyed.60% of retinoblastomas occur sporadically, about 40% familial. The RB protein encloses in a shell-like fashion the transcription factor E2F, which is necessarily needed to initiate S phase.

Tumor suppressor gene p53: The encoded protein is a DNA-binding protein found in the nucleus. By preventing damaged cells from dividing or inducing apoptosis, p53 acts as a tumor suppressor protein. Mutations of this gene represent the most common genetic alterations in human tumors ever. In more than 50% of malignant tumors, p53 mutations with loss of function are detected.

P16 protein: specifically inhibits the complex formed by CDK4 and cyclin-D, which controls the passage through the G1 phase of the cell cycle by phosphorylating the Rb (retinoblastoma) protein. Of the genes involved in the cell cycle, P16 is by far the most frequently altered in carcinomas.

P27 protein: controls the passage from G0 to G1 phase of the cell cycle; when increased, it prevents it. Both virally infected cells and neighboring cells (via the pathway of contact inhibition) promote the formation of P27 via TGF-beta.P53 protein: ensures that a cell only divides if its genetic material is also intact. This is not the case in a tumor cell. In this case, the P53 protein shows its two main effects: the cell cycle arrest or, in the case of irreparable damage, the initiation of apoptosis (see below transcription genes).

The functions of tumour suppressor genes can be subdivided into:

• suppression of the gene expression of growth factors with resulting inhibition of the cell cycle or arrest of the cell cycle in case of DNA damage. In case of reversible damage, continuation of the cell cycle.
• In case of irreversible DNA damage, the gene initiates apoptosis of the cell. Some proteins involved in cell adhesion prevent tumour cells from invading and thus inhibit the formation of metastases.