Tumor suppressor genes = anti-oncogenes
Mutations in tumor suppressor genes are recessive in that one good copy protects
against cancer.
In contrast, a mutated proto-oncogene or a viral oncogene is dominant in that
only one bad gene is necessary to cause cancer.
p 53 and RB are anti-oncogenes.
- In cell culture their gene products reverse the action of known oncogenes.
- More than half of all human cancers do, in fact, harbor p53 mutations and
have no functioning p53 protein.
- Mutations in p53 are recessive- one normal gene and one mutated genes predisposes
to cancer (in contrast oncogenes are dominant - the presence of one normal
gene (proto-oncogene) and one mutated gene (oncogene) the oncogene presisposes
to cancer)
p53
The product of the tumor suppressor gene p53 is a protein with a molecular weight
of 53 kilodaltons (hence the name).
- prevents a cell from completing the cell cycle if its DNA is not properly
replicated in S phase.
- binds to a transcription factor called E2F.
- prevents E2F from binding to the promoters of such proto-oncogenes as c-myc
and c-fos.
- c-myc and c-fos is needed for mitosis
- blocking the transcription factor needed to turn on c-myc and c-fos prevents
cell division.
- The p53 protein also triggers programmed cell death (apoptosis) if the damage
to the cell is too great to be repaired.
E6, a gene product from the papilloma virus, binds to p53 and targets it for
destruction (proteolytic enzymes hydrolyse it), therefore p53 cannot bind to
the cellular transcription factor E2F that is necessary for cell division. E2F
causes other transcription factors such as c-myc to be transcribed. c-myc is
necessary for transcribing genes that tell cells to divide.
RB
RB binds to E2F and prevents E2 from turning on genes necessary for cell division