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A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. [1] If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function.
The key target of Mdm2 is the p53 tumor suppressor. Mdm2 has been identified as a p53 interacting protein that represses p53 transcriptional activity. Mdm2 achieves this repression by binding to and blocking the N-terminal trans-activation domain of p53. Mdm2 is a p53 responsive gene—that is, its transcription can be activated by p53.
Its role as a tumor suppressor gene was revealed in 1989 by Bert Vogelstein at the Johns Hopkins School of Medicine and Arnold Levine at Princeton University. [ 80 ] [ 81 ] p53 went on to be identified as a transcription factor by Guillermina Lozano working at MD Anderson Cancer Center .
p14ARF (also called ARF tumor suppressor, ARF, p14 ARF) is an alternate reading frame protein product of the CDKN2A locus (i.e. INK4a/ARF locus). [ 1 ] p14ARF is induced in response to elevated mitogenic stimulation, such as aberrant growth signaling from MYC and Ras (protein) . [ 2 ]
It was later found that carcinogenesis (the development of cancer) depended both on the mutation of proto-oncogenes (genes that stimulate cell proliferation) and on the inactivation of tumor suppressor genes, that keep proliferation in check. Knudson's hypothesis refers specifically, however, to the heterozygosity of tumor suppressor genes.
Oncogenomics is a sub-field of genomics that characterizes cancer-associated genes.It focuses on genomic, epigenomic and transcript alterations in cancer. Cancer is a genetic disease caused by accumulation of DNA mutations and epigenetic alterations leading to unrestrained cell proliferation and neoplasm formation.
Some suggest that the TP73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). This is a strong theory and causes much confusion, as it is unknown which of the two p73 variants is over-expressed and ultimately plays a role in tumorigenesis. Genes of the p53 family are known to be complex.
Tumor suppressor genes are genes that inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Finally Oncovirinae, viruses that contain an oncogene, are categorized as oncogenic because they trigger the growth of tumorous tissues in the host.