Tice these days to test whether a phosphate at a site

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tice these days to test whether a phosphate at a site activates (or inactivates) a protein by engineering a version of the protein with a glutamate at that position. Often (but not always) the glutamate change will mimic the effect of the phosphate. Reference: Wang L, Cunningham JM, Winters JL, Guenther JC, French AJ, Boardman LA, Burgart LJ, McDonnell SK, Schaid DJ & Thibodeau SN (2003) BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 63, 5209–5212. 20–54 These observations argue strongly that MMTV generates an oncogene upon integration into the mouse genome. It is extremely unlikely that MMTV would integrate so often in the same region of the genome by chance. More- over, a unique transcript is generated in the region of the integrated virus, THE MOLECULAR BASIS OF CANCER-CELL BEHAVIOR A465
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suggesting that a gene is turned on in response to the neighboring viral sequences. These results summarize the initial characterization of the Int1 locus in mice. It was later shown to be homologous to the wingless locus in Drosophila , both of which are now referred to as Wnt genes. These genes secrete a signaling molecule that triggers a signaling pathway in other cells that activates expression of a set of Wnt-responsive genes, some of which promote cell proliferation. Reference: Nusse R & Varmus HE (1982) Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31, 99–109. CALCULATIONS 20–55 A. Four different haploid gametes can combine to give 16 different diploid products. Of the several different ways of representing these possibilities, the most concise is the Punnett square, a time-honored tradition with geneticists (Table 20–3). However the possibilities are represented, the 16 combinations of gametes form 9 distinct genotypes. Four genotypes are rep- resented once (the ones along the diagonal from upper left to lower right in Table 20–3). One genotype is represented four times (the one along the diag- onal from lower left to upper right). The remaining genotypes are each rep- resented twice (symmetrically arrayed about the diagonal from upper left to lower right). The ratios of the genotypes, along with their expected frequen- cies among 36 progeny, are given in Table 20–4). Progeny with the genotypes p53 +/+ Mdm2 –/– and p53 +/– Mdm2 –/– are under-represented in these experiments: none were found. More detailed experiments have shown that these mice do not survive because they die early in embryonic development. B. It is striking that p53 +/+ Mdm2 –/– and p53 +/– Mdm2 –/– do not survive, whereas p53 –/– Mdm2 –/– mice do. In the absence of Mdm2, it seems that even a haploid amount of p53 is lethal. Since Mdm2 is a ubiquitin ligase, one reasonable explanation for this result is that Mdm2 normally keeps the cel- lular concentration of p53 very low. In the absence of Mdm2, p53 is no longer destroyed at the proper rate and accumulates to levels that are toxic.
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