|
The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''RB'' or ''RB1'') is a tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle progression. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases. Rb belongs to the pocket protein family, whose members have a pocket for the functional binding of other proteins. Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomaviruses, bind and inactivate pRb, this can lead to cancer. == Name and genetics == In humans, the protein is encoded by the RB1 gene located on 13q14.1-q14.2. If both alleles of this gene are mutated early in life, the protein is inactivated and results in development of retinoblastoma cancer, hence the name ''Rb''. Retinal cells are not sloughed off or replaced, and are subjected to high levels of mutagenic UV radiation, and thus most pRB knock-outs occur in retinal tissue (but it's also been documented in certain skin cancers in patients from New Zealand where the amount of UV radiation is significantly higher). Two forms of retinoblastoma were noticed: a bilateral, familial form and a unilateral, sporadic form. Sufferers of the former were 6 times more likely to develop other types of cancer later in life. This highlighted the fact that mutated Rb could be inherited and lent support to the two-hit hypothesis. This states that only one working allele of a tumour suppressor gene is necessary for its function (the mutated gene is recessive), and so both need to be mutated before the cancer phenotype will appear. In the familial form, a mutated allele is inherited along with a normal allele. In this case, should a cell sustain only ''one'' mutation in the other RB gene, all Rb in that cell would be ineffective at inhibiting cell cycle progression, allowing cells to divide uncontrollably and eventually become cancerous. Furthermore, as one allele is already mutated in all other somatic cells, the future incidence of cancers in these individuals is observed with linear kinetics. The working allele need not undergo a mutation ''per se'', as loss of heterozygosity (LOH) is frequently observed in such tumours. However, in the sporadic form, both alleles would need to sustain a mutation before the cell can become cancerous. This explains why sufferers of sporadic retinoblastoma are not at increased risk of cancers later in life, as both alleles are functional in all their other cells. Future cancer incidence in sporadic Rb cases is observed with polynomial kinetics, not exactly quadratic as expected because the first mutation must arise through normal mechanisms, and then can be duplicated by LOH to result in a tumour progenitor. RB1 orthologs have also been identified in most mammals for which complete genome data are available. RB/E2F-family proteins repression transcription. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Retinoblastoma protein」の詳細全文を読む スポンサード リンク
|