You have discovered two new inhibitors that inhibit enzymes involved in the pathway shown below. Both inhibitors are newly identified proteins. Youknow that one of these proteins is a noncompetitive inhibitor of the G1/S-cyclin dependent kinase (G1/S-Cdk). Another protein is a competitive inhibitorof the phosphatase (ie. a regulatory enzyme) that removes phosphates from phosphorylated Rb.mitogenactivated mitogen receptorintracellularsignalingpathwayactivated G,-Cdkand G,/S-čdkinactivatedRb proteinactive Rbproteininactivatedtranscriptionregulatoractive transcriptionregulatorPHOSPHORYLATIONOF RbTRANSCRIPTIONTRANSLATIONCELLPROLIFERATION1. What effect would the noncompetitive inhibitor of the G1/S-Cdk complex have on the Rb protein in the pathway shown above? And what effectwould that have on the final outcome for these cells?2. What effect would the competitive inhibitor of the phosphatase that acts on phosphorylated Rb have on the final outcome for these cells?3. Which of the inhibitors would you prescribe to a cancer patient and why?

Rb protein suppresses tumor cell growth, it plays a key role in the G1 checkpoint of the cell cycle…

1. What effect would the noncompetitive inhibitor of the G1/S-Cdk complex have on the Rb protein in the pathway shown above? And what effect would that have on the final outcome for these cells? 2. What effect would the competitive inhibitor of the phosphatase that acts on phosphorylated Rb have on the final outcome for these cells? 3. Which of the inhibitors would you prescribe to a cancer patient and why?

1. What effect would the noncompetitive inhibitor of the G1/S-Cdk complex have on the Rb protein in the pathway shown above? And what effect would that have on the final outcome for these cells? 2. What effect would the competitive inhibitor of the phosphatase that acts on phosphorylated Rb have on the final outcome for these cells? 3. Which of the inhibitors would you prescribe to a cancer patient and why?

Biochemistry

9th Edition

ISBN:9781319114671

Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Chapter1: Biochemistry: An Evolving Science

Section: Chapter Questions

Problem 1P

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4. To understand the function of the Bcl11a protein, scientists attempted to knockdown its expression by transfecting human cells in culture with siRNA targeting the Bcl11a gene. A. Briefly describe the first step of the pathway initiated by siRNA entering the cytoplasm. Following transfection of cells with two different siRNA sequences complementary to the Bcl11a gene (siRNA 1 and siRNA 2), the level of Bcl11a protein expression was measured by western blot. The researchers also included a positive control to measure actin, a housekeeping gene. In a western blot experiment*, how do scientists B. specifically detect a protein of interest on a nitrocellulose membrane? Control siRNA 1 C. Which siRNA sequence was more effective at targeting Bcl11a expression? Briefly explain your answer. siRNA 2 BCL11A Actin
There are many compounds that have been advertised to reduce or delay aging. Resveratrol is a compound isolated from red grapes, and can be found in red wine. This compound is thought to have substantial effects in mammals, such as preventing the growth of tumors and reducing age-related diseases. Many studies have shown that resveratrol and its derivatives cause a cell-cycle arrest in S phase and induce apoptosis. A series of cultured cells have been analyzed for DNA content in the presence and absence of these compounds using a flow cytometer. Using the controls cells (dashed line), which of the following histograms better represents the DNA content of cells treated with the compounds? The X-axis shows relative DNA content.
could you explain a bit more what this sentences mean: The information displayed demonstrates a significant increase in cell proliferation inside the dentate gyrus of mice that were locked in voluntary exercise compared to the control group. The use of 5-Bromo-2'-deoxyuridine (BrdU), a thymidine analog, permits the following of recently formed cells because it is incorporated into the DNA of dividing cells amid the S stage of the cell cycle. The immunocytochemical examination uncovered a 67% increase in BrdU-labeled cells within the running group, meaning upgraded neurogenesis, which is factually noteworthy as shown by the p-value of 0.0001. The observation that the runner group effectively utilized the running wheels given in their cages relates to the increment in BrdU-labeled cells.
6. Vampire bats are mammals that consume blood as their only source of nutrients. Because blood is rich in iron, it is necessary for the digestive system of the vampire bat to manage excess iron. Like humans, ferritin and transferrin receptor gene products are expressed by the vampire bat genome and function to maintain iron homeostasis. Ferritin A. The iron response element (IRE) binding protein is able to regulate expression of both ferritin and transferrin receptor genes. What feature of these genes allows for specific regulation by the IRE binding protein? B. How is activity of the IRE binding protein regulated? C. In an environment with excess iron, what levels of mRNA and protein do you expect to detect of Ferritin and Transferrin receptor? Briefly explain. Explanation Transferrin receptor RNA levels ( ) high ( ) low ( ) high ( ) low Protein levels () high levels ( ) low levels () high levels ( ) low levels
8. Describe the MAP kinase activation pathway
one answer per question
Vinblastine is a standard chemotherapeutic drug used to treat cancer. Because it interferes with the assembly of microtubules, its effectiveness must be related to Select one: a. inhibition of DNA synthesis. O b. myosin denaturation and inhibition of cleavage furrow formation. c. suppression of cyclin production. Od. inhibition of regulatory protein phosphorylation. O e. disruption of mitotic spindle formation. Next page
31. “Wnt”is a regulatory factor that regulate myogenic stem cell proliferation? True False
7. Researchers obtain a pure solution of antibodies that bind specifically to the cadherins (linking proteins) of the desmosomes of epithelial cells of a mouse. They then take a culture of these cells, divide it into separate control and experimental tubes, and add antibodies to the experimental tube and an equal volume of water to the control tube. What is the predicted outcome of this experiment? A. Cells in the experimental tube will adhere to each other, but cells in the control tube will not B. Cells in both tubes will adhere to each other C. Cells in neither tube will adhere to each other D. Cells in the control tube will adhere to each other, but cells in the experimental tube will not
4. You develop the covalently-acting irreversible kinase inhibitor ibrutinib shown on the left that reacts potently with a cysteine in the ATP binding pocket of the cancer-promoting kinase Bruton's Tyrosine Kinase (BTK). You would like to know whether ibrutinib engages and selectively targets BTK in vivo in the tumor of a mouse model of cancer. Describe experimentally how you would use activity-based protein profiling to assess whether ibrutinib inhibited BTK in vivo in the tumor and also determine how selectively ibrutinib engaged BTK compared to other kinases in the tumor? ( NH₂ H₂N- ibrutinib OH OH OH OH OH activity-based probe for kinases that covalently modifies active-site lysine of all kinase ATP binding pocket L W ta to C с
7. Explain why a mutant Ras is an oncogene causing many human cancers
3) The tumor suppressor protein Rb regulation of the entry into the S phase of the cell cycle is represented in this diagram. DNA Answer: b) Explain your choice above: Answer: Rb E2F Genes needed for S phase are NOT transcribed Growth factor Ras pathway Cdk-cyclin 30 ATP ADP Phosphorylated Rb protein P Rb E2F Gene transcription a) In hereditary retinoblastoma tumors, Rb is mutated. Among the following mutations, which one is not likely to be found in these tumors. 1) Mutation prevents Rb to bind E2F by modifying the binding site. 2) Mutation prevents Rb to be dephosphorylated and recycled (possibly by prevented phosphorylated Rb to be recognized by the phosphatase that removes its phosphates). 3) Mutation may cause Rb to be misfolded and not have a functional conformation 4) Mutation that prevent Rb to be phosphorylated by cdk-cyclin. 5) Mutation may cause Rb to be unstable and degraded rapidly. c) (4 pts) Human papilloma virus (HPV) infections are the main causes of cervical cancers.…