Many currently marketed drugs exert their pharmacological effects by binding to ligand-activated transcription factors and modulating gene expression. One example, are various drugs that target the estrogen receptor to treat breast cancer, osteoporosis and post-menopausal symptoms. Below is a ChIP experiment examining the effects of no drug treatment (C), the natural hormone estrogen (E) and the drugs tamoxifen (T) and raloxifene (R) on recruitment of coactivators (SRC-1 and CBP), Histone Deacetylase Complexes (HDACs) and acetylation of histones associated with the C-myc gene. Which of the following statements are correct based on this data (select all that apply)?

Suppose that Protein J which is a hypothetical protein kinase receptor was determined to be related to the progression of cancer through its activation. It was also determined that the protein exists in the active and inactive forms. The said active form is highly similar to the Protein K's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized to inhibit Protein J. The affinities of the ligands are shown in the table. Kp values Active Protein J Inactive Protein J Protein K Ligand A 10 mM 20 nM 5 mM Ligand B 20 nM 10 mM 15 nM Ligand C 20 nM 15 nM 15 nM Question: Describe the relative binding affinities of Ligand A to Protein K and to the active and inactive forms of Protein J. Determine which will Ligand A bind with the highest, medium, and lowest affinity.

Suppose that Protein J which is a hypothetical protein kinase receptor was determined to be related to the progression of cancer through its activation. It was also determined that the protein exists in the active and inactive forms. The said active form is highly similar to the Protein K's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized to inhibit Protein J. The affinities of the ligands are shown in the table. Kp values Active Protein J Inactive Protein J Protein K Ligand A 10 mM 20 nM 5 mM Ligand B 20 nM 10 mM 15 nM Ligand C 20 nM 15 nM 15 nM Question: a. Which of the ligands, based on the table, may be expected to be the most potent or have the highest activity against cancer? Explain. b. Which of the ligands, based on the table, may be expected to be least toxic to normal cells? Explain.

You wish to find the cis-acting regulatory DNA elements responsible for the transcriptional responses of two genes, c-fos and globin. Transcription of the c-fos gene is activated in response to fibroblast growth factor (FGF), but it is inhibited by cortisol (Cort). On the other hand, transcription of the globin gene is not affected by either FGF or cortisol, but it is stimulated by the hormone erythropoietin (EP). To find the cis-acting regulatory DNA elements responsible for these transcriptional responses, you use the following clones of the c-fos and globin genes, as well as two “hybrid” combinations (fusion genes), as shown in the diagram below. The letter A represents the intact c-fos gene, D represents the intact globin gene, and B and C represent the c-fos–globin gene fusions. The c-fos and globin exons (E) and introns (I) are numbered. For example, E3(f) is the third exon of the c-fos gene and I2(g) is the second intron of the globin gene. (These labels are provided to help you…

Describe two roles for polyubiquitinylation in the NF-κB signaling pathway

Explain, in detail, how tyrosine kinase proteins are involved in one signal transduction pathway of your choice. Make sure you describe the complete pathway in which it is involved. Then, describe how you would experimentally demonstrate the requirement of a tyrosine kinase protein in your chosen pathway.

If we knock out a gene, it can tell us something about how important that gene is or if other genes can compensate for its absence in a complex. To further establish the role of PSEN1 and PSEN2 in early onset Alzheimer's disease they are individually knocked out in mouse models. Knockout of PSEN1 leads to an embryonic lethal phenotype and dramatically reduced Aß levels. However knockout of PSEN2 gives no obvious phenotype and essentially normal AB levels. Question 16) Which of the following hypotheses does this observation support? [10 Marks] Under normal circumstances y-secretase complexes contain equal ratios of PSEN1 and PSEN2 b. The knockout of PSEN1 and PSEN2 didn't work O c. a. Under normal circumstances y-secretase complexes primarily contain PSEN2 rather than PSEN1 d. Under normal circumstances y-secretase complexes primarily contain PSEN1 rather than PSEN2 e. Under normal circumstances y-secretase complexes do not contain either PSEN1 or PSEN2