a mutation in p53 leads to alpha thalassemia abnormal morphogenesis.
a mutation in p53 leads to alpha thalassemia abnormal morphogenesis.
what does a mutation in p53 lead to?
alpha thalassemia abnormal morphogenesis
the large spectrum of cancer phenotypes due to mutations in the "tp53" gene is also supported by the fact that different isoforms of p53 proteins have different cellular mechanisms for prevention against cancer. mutations in "tp53" can give rise to different isoforms, preventing their overall functionality in different cellular mechanisms and thereby extending the cancer phenotype from mild to severe. recents studies show that p53 isoforms are differentially expressed in different human tissues, and the loss-of-function or gain-of-function mutations within the isoforms can cause tissue-specific cancer or provides cancer stem cell potential in different tissues. tp53 mutation also hits energy metabolism and increases glycolysis in breast cancer cells.
p53
wild-type p53 has been shown to repress survivin expression at the mrna level. using an adenovirus vector for wild-type p53, human ovarian cancer cell line 2774qw1 (which expresses mutant p53) was transfected. mrna levels of survivin were analyzed by real-time quantitative pcr (rt-pcr) and showed time-dependent down regulation of survivin mrna levels when the cells were infected with wild-type p53. a 3.6 fold decrease of survivin mrna level was observed 16 hours after infection initiation and decreased 6.7 fold 24 hours after infection. western blot results do show that there is indeed the p53 from the adenoviral vector was being expressed in the cells using antibody specific for p53. the expression of p53 levels indicative of its role in survivin repression shows that p53 started to be expressed 6 hours into infection and had its highest level at 16–24 hours. to further confirm that endogenous wild-type p53 is really causing the repression of survivin gene expression, the authors induced a549 (human lung cancer cell line with wild-type p53) and t47d (human breast cancer cell line with mutant p53) cells with dna-damaging agent adriamycin to trigger the physiological p53 apoptotic response in these cancer cells and compare the survivin levels measured to the same cells without dna damage induction. the a549 line, which intrinsically has functioning wild-type p53, showed significant reduction in survivin levels compared to non-induced cells. this same effect was not seen in t47d cells that carry mutant inactive p53.
survivin