Biochemistry: The Molecular Basis of Life
6th Edition
ISBN: 9780190209896
Author: Trudy McKee, James R. McKee
Publisher: Oxford University Press
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Chapter 18, Problem 59SA
Summary Introduction
To explain:
The retinoblastoma tumor suppressor gene and the transcription activating dimer form a complex thatconscriptshistone deacetylase to chromatin.
Introduction:
The retinoblastoma protein (pRB) is also known as the tumorsuppressor protein. It is coded by the retinoblastoma tumorsuppressor gene Rb. It is an antioncogene that defends the cell against cancer. Its main function is to inhibit the proliferation of celland promote the death of the defected cells.
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The tumor suppressor pRB also binds to and suppresses theactivity of retinoblastoma binding protein 2 (RBP2), ahistone demethylase that removes methyl groups from diand trimethylated lysines in histone 3. What is the possibleconsequence of an inactivating mutation in RB1 that causesan inability of pRB to bind RBP2?
The retinoblastoma tumor suppressor gene Rb (RB1) codes forthe retinoblastoma protein (pRB). pRB prevents the progression of the cell cycle through G1 if DNA has been damaged. Itdoes so in part because it binds a transcription-activatingdimer referred to as E2F-DP. The pRB-E2F/DP complex recruits a histone deacetylase to chromatin. Explain.
When an injury occurs to the skin, the epithelial cells near the wound are signaled to react (by proliferating, migrating, and/or differentiating) to restore the skin in the wound. To investigate the healing process, researchers removed a small area of epithelial cells from the skin of mice, causing a wound. The researchers monitored the acetylation status of histone H4 at lysines K5, K8, and K16 on days 1, 4 and 9 after the wound was made. Cells in three regions were studied (see Figure A below):
Normal epithelial cells not directly near the wound
Epithelial cells adjacent to the wound
The cells repopulating/repairing the wound (referred to as an “epithelial tongue” early in the process and “closed wound” later in the process)
The percent of cells that were positive for H4 acetylation was recorded. The bar graph in Figure B below shows data for Days 4 and 9 for cells examined in the wound.
While this experiment focused on mice, we may be able to apply the results to…
Chapter 18 Solutions
Biochemistry: The Molecular Basis of Life
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- Tumor cells from a person with leukemia have been analyzed to determine which oncogene is involved in the transformation. After partial sequencing of the gene, the predicted gene product is identified as a tyrosine kinase. Which of the following proteins would most likely be encoded by an oncogene and exhibit tyrosine kinase activity? A. Nuclear transcriptional activator B. Epidermal growth factor C. Membrane-associated G protein D. Platelet-derived growth factor E. Growth factor receptorarrow_forwardTranscriptionally active chromatin are generally found near the outer regions of the nucleus near the membrane. true or false?arrow_forwardATM is a kinase that phosphorylates histone H2AX in response to double-stranded DNA breaks. Which of the following scenarios would most quickly regulate ATM activity in the cell? a) Adding silencing methyl groups to cytosines in the Atm gene b) Modifying the histone code for the Atm gene c) Increasing expression of a miRNA specific for the Atm mRNA d) Activating an E3 ubiquitin ligase specific for the ATM proteinarrow_forward
- For each of the following situations, provide a plausible explanation for how it could lead to unrestricted cell division.(a) Colon cancer cells often contain mutations in the gene encoding the prostaglandin E2 receptor. PGE2 is a growth factor required for the division of cells in the gastrointestinal tract.(b) Kaposi sarcoma, a common tumor in people with untreated AIDS, is caused by a virus carrying a gene for a protein similar to the chemokine receptors CXCR1 and CXCR2. Chemokines are cell-specific growth factors.(c) Adenovirus, a tumor virus, carries a gene for the protein E1A, which binds to the retinoblastoma protein, pRb. (d) An important feature of many oncogenes and tumor suppressor genes is their celltype specificity. For example, mutations in the PGE2 receptor are not typically found in lung tumors. Explain this observation. (Note that PGE2 acts through a GPCR in the plasma membrane.)arrow_forwardWhich of the following does NOT pertain to the myoblast-determining gene 1?*a. It is a master gene.b. It is a silencing gene.c. It produces a transactivating protein.d. It activates its own gene. Gene silencing involves which type of histone modification?* a. acetylation of histone 4 b. dimethylation of histone 3 c. trimethylation of histone 4 d. trimethylation of histone 3 Given the required environment, the totipotency of the nucleus can allow which of the following?* a. a committed cell to undergo dedifferentiation b. a committed cell to undergo terminal differentiation c. a terminally differentiated cell to produce a complete organism d. a terminally differentiated cell to produce specific types of tissues An induced pluripotent cell is described by which of the following?* a. It is a committed cell that undergoes redifferentiation. b. It is a committed cell that undergoes dedifferentiation. c. It is a terminally…arrow_forwardThe rb gene encodes a protein that inhibits E2F, a transcriptionfactor that activates several genes involved in cell division.Mutations in rb are associated with certain forms of cancer,such as retinoblastoma. Under each of the following conditions,would you expect the cancer to occur?A. One copy of rb is defective; both copies of E2F are functional.B. Both copies of rb are defective; both copies of E2F arefunctional.C. Both copies of rb are defective; one copy of E2F is defective.D. Both copies of rb and E2F are defective.arrow_forward
- Is the presence of oncogenic Ras necessary for transient inflammatory stimulation to induce chronic pathologies (such as cancer) OR is chronic inflammation essential for oncogenic Ras to induce tumorigenesis?arrow_forwardAn old genetic observation is that a normally active gene will be silenced if it is moved by transposition or crossing over from an uncondensed (euchromatic) region to a heavily condensed (heterochromatic) region of a chromosome. Assume the euchromatic chromatin containing the active gene is surrounded by heterochromatic chromatin immediately after insertion. Please explain in terms of the control of histone modification why the normally active gene is silenced when it becomes surrounded by condensed regions. (Do not explain how histone modification causes chromatin condensation.)arrow_forwardBecause DNA is found in the nucleus, transcription is a nuclear-localized process. Ribosomes responsible for protein synthesis are found in the cytoplasm. Why is hnRNP trafficking to the cytoplasm restricted to the nuclear pore complexes?arrow_forward
- . Please explain the regulatory role of Bcl-2 family proteins in cell death?arrow_forwardWhat effect would inhibitors of histone deacetylases have upon transcription? Group of answer choices They would increase transcription by making the chromatin more compact They would increase transcription by making the chromatin less compact They would decrease transcription by making the chromatin more compact They would decrease transcription by making the chromatin less compact For this question, we will consider a eukaryotic mRNA that has four exons (E1, E2, E3, E4) and three introns (I1, I2, I3). What could occur if a protein were to bind over the 3' splice site of intron 2 (I2)? Group of answer choices The processed mRNA would consist of: E1+E2+E3+E4 The processed mRNA would consist only of: E1+E3 The processed mRNA would consist only of: E3+E4 The processed mRNA would consist of: E1+E2+E4arrow_forwardA drug called garcinol, is isolated from Garciniaindica (a fruit-bearing tree commonlyknown as kokum), is a potent inhibitor of histone deacetylase. Would you expect thisdrug to enhance or inhibit transcriptional initiation and elongation?arrow_forward
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