Tumor Suppressor Gene
Tumor suppressor gene is also called antioncogene. It refers to a gene that offers protection to a cell from a single step on cancer’s path. If tumor suppressor gene mutates casing a reduction or loss in its role or function, this can cause the cell to progress into cancer. Usually, this occurs in combination with various genetic changes.
Losing these genes can even be important that oncogene or proto-oncogene activation for formation of different types of cancer cells in humans. Tumor suppressor genes may be grouped in different categories including gatekeeper genes, landscaper genes and caretaker genes. This classification changes as the fields of learning such as genetics, epigenetic, molecular biology and medicine advances.
Compared to oncogenes, the tumor suppressor gene generally follow two-hit hypothesis. This means that the alleles coding for particular protein has to be affected prior the manifestation of an effect. This is due to the fact that if one allele of the gene sustains some damage, the second allele will still produce correct protein. Thus, alleles that suppress mutant tumor are recessive while alleles for mutant oncogene are dominant.
A.G Knudson proposed the two-hit hypothesis for the first time for retinoblastoma cases. Knudson observed the age of the onset of the retinoblastoma and this was followed by the second order kinetics. This implied that it was important to have two genetic events that were independent.
Knudson recognized that two hit hypothesis was consistent with the recessive mutation that involved single gene. However, it required biallelic mutation. In contrast, oncogene mutations generally involve single allele since they are considered as gain-of-function mutations.
When it comes to two-hit rule, tumor suppressor gene has exceptions such as specific mutations in p53 gene product. The p53 mutations are capable of functioning as dominant negative. This implies that mutated p53 protein is capable of preventing function of a normal protein from un-mutated allele. Other tumor suppressors that are considered as exceptions to two hit rule include those exhibiting haploinsufficiency such as NF in neurofibroma and PTCH in the medulloblastoma.
More precisely, tumor suppressor genes code for proteins that either have repressive or dampening effect on regulation of cell cycle or even they promote apoptosis in some cases or they can do both. Functions of the proteins of tumor suppressor genes are usually classified into various categories. These include genes repression, coupling, and initiating apoptosis when damage is irreparable, cell adhesion which prevents dispersing of tumor cells, and DNA repair.
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