RIBOSOMAL PROTEIN MUTATIONS AND p53 LOSS
The one of the most popularly studied organism for analysis of mutations of proteins is zebrafish (Danio rerio).Ribosomal protein mutations are seen in patients suffering from severe anemia or other cell death associated disorders. These mutations have been extensively identified in model organisms like zebra fish. The zebrafish full length p53 protein is 48% identical to the human p53 protein and is highly expressed in embryos. Hence, a study of these intricate relations is carried out in zebrafish.
Ribosomal protein gene is vastly studied in zebrafish for haplosufficiency. Ribosomal protein mutations are seen in patients suffering from Diamond Blackfan anaemia which shows red cell aplasia and bone marrow failure syndrome. As stated earlier, impairment of RP synthesis or mutations in RP can cause stabilization of p53 due to which apoptosis of cells is induced. (Warner & Mckintosh, 2009). In contrast to this observation in humans, it is seen that in zebrafish, p53 is unable to stabilize in spite of ribosomal haplosufficiency and presence of ionizing radiations. This paved the way for an interesting aspect of relationship between ribosomal mutations and p53 regulation. (Antunes et
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The prominent mechanisms observed in these relationships are discussed below.
In zebra fish, mutations involved in ribosomal proteins, from both small and large subunits, give rise to a rare type of tumor, known as malignant peripheral nerve sheath tumors (MPNSTs). It is seen that loss of function point mutation of p53 (M214K) also gives the same type of tumor morphology.
Therefore, the involvement of ribosomal protein mutations in tumor formation via a p53 degradative mechanism is a prominent possibility. A study was conducted in this regard to identify the link between p53 and ribosomal
In vitro: Previous study found that the exposure of the tumor cell lines to 3-AP before or immediately after irradiation resulted in an increase in radiosensitivity. In contrast, 3-AP could enhance the radiosensitivity of the normal fibroblast cell line only when the exposure was before irradiation. There were no consistent differences between cell lines with respect to the expression of the RR subunits. Whereas
Minggang Fang, Fen Xia, Meera Mahalingam, Ching-Man Virbasius, Narendra Wajapeyee and Michael R. Green. (May, 2013) INTRODUCTION: MEN1 is a protein localized in the nucleus that is known to assist in various cellular activates involving cell cycle regulation, transcription, and cellular proliferation. Mutations in the MEN1 gene that result in its loss of function are linked to multiple endocrine neoplasia type 1. This type of familial cancer syndrome is an inherited autosomal dominant disease which results in an increased
In vitro: Treatment of MM cells with SRT1720 inhibited growth and induced apoptosis in MM cells resistant to bortezomib therapy without significantly affecting the viability of normal cells. Mechanistic studies demonstrated that anti-MM activity of SRT1720 is associated with activation of caspase-3, caspase-8, caspase-9, poly(ADP) ribose
Blackfish, a documentary by Gabriela Cowperthwaite, a historically observed impact of the captivity of killer whales. This Documentary focuses on the orca Tilikum, who was captured off the coast of Iceland. On February 21, 1991, Sealand trainer Keltie Byrne fell into the pool with Tilikum. She was pulled to the bottom by Tilikum, tossed around, and drowned. It took Sealand employees two hours to recover her.
In May 1991, zebra mussels were found in the Hudson River. 500 billion of these mussels were found in the course of a year. They looked seemingly harmless, but over time these mussels became a sort of threat. They were destroying the microscopic animals in the river. On the other hand, they also help out by a ton.
Invasive species are “species that is non-native to the ecosystem whose introduction is likely to cause economic and environmental harm”. A example of Invasive species would be the Zebra Mussel. Zebra Mussels or also known as Dreissena polymorpha is a small freshwater mussel. The Zebra Mussels can live up to three-nine years which can grow up to 2 inches. These mussels attach to hard surfaces such as rocks or boats.
In the late 1940s, scientific research began taking off as innovative technologies and diseases were being created and discovered. One important field of study during the time was cancer. Like many types of new research, there were a few problems getting the ball on the roll. One problem scientists faced was obtaining cancerous cells that would stay long enough to study. One scientist struggled with this until a particularly unique strand of cells came along.
There are some pretty bad things going on in the Hudson river. Have you ever seen a zebra mussel. Or even let alone heard of these kinds of creatures. Well let me tell you exactly what is going on in the Hudson river. It’s also very sad as well because entire ecosystem is going down with the recent crazy population of the mussels.
THE ZEBRA MUSSEL INCIDENT The Zebra Mussel Incident Zebra Mussels are an invasive species which now dominate the Great Lakes region, they were introduced in the 1980’s and ever since then their quantities have increased dramatically. Since the time they arrived they have caused many problems including problems in the ecosystem and with the economy. Human’s have been trying ever since their arrival to eliminate or reduce their quantities but not much progress has been made. Right now Zebra Mussels are one of the biggest issues affecting the great lakes.
Zebra Mussels are invasive species who came to canada accidentally by ballast water ship. This invasive species arrived to canada at late 1980’s came to Ontario and Quebec and it first came to lake St.Clair and get speared to south to Gulf of Mexico and further speared to southern Canada. This invasive species Zebra Mussels is native Caspian region. Zebra mussels lay 1,000,000eggs per years. Zebra mussels are bad for Canadian environment because it eat all the food for fishes and then their will be no food for fishes to eat and then fishes will get extinct that’s cause fishes to extinct.
In my hypothesis, I state that the stickleback fish would not have a pelvic spine caused by an insertion mutation in the Pitx1 enhancer region. According to the gel, the stickleback fish in Big Lake do not have the pelvic spine due to a deletion mutation found in the Pitx1 enhancer region. This can be further proved by the phenotype of the fish found in Big lake. The stickleback fish found in Big Lake (seen in figure 2) is smooth across the bottom, with no pelvic spine present. This proof supports the results of the gel
ibly through the positive regulation of transcription factor Foxd3.2,3 Preliminary data support this finding, but they also reveal a more global effect on neural crest along the A-P axis resulting from aberrant expression of hoxb5b, a zebrafish
Most of them are responsible for energy production in mitochondria by reducing or eliminating the action of the protein complexes in ATP production. Decrease in cellular energy may lead to cell death, especially in the tissue that requires large amount of energy, e.g. brain, heart and muscles. Two of the most frequently mutated genes in Leigh syndrome are SURF1 gene and MT-ATP6
EPO is a hormone which is required for the proliferation erythrocytes and undergoes hypoxia induced transcription (Semenza et al., 1991, Goldberg et al., 1988). HIF-1 complex is a master regulator of the transcription factor, which is comprises of two heterodimeric protein subunits i.e. α and β subunits (Wang et al., 1995). β subunit is identified as a binding partner of the aryl hydrocarbon receptor (Reyes et al., 1992) so it is also known as ARNT (the aryl hydrocarbon nuclear translocator). Both of the subunits of HIF-1 complex belong to the same family of proteins that contain basic helix-loop-helix (HLH) and PER-ARNT-SIM (PAS) motifs. These two motifs are important for the formation of heterodimerisation between the HIF-α and HIF-β subunits (Manolescu et al., 2009).
Cell viability assay: Introduction. Methods in Molecular Biology 740: 1-6. ThermoFisher Scientific. [Internet].