Genetics: From Genes to Genomes, 5th edition
Genetics: From Genes to Genomes, 5th edition
5th Edition
ISBN: 9780073525310
Author: Leland H. Hartwell, Michael L. Goldberg, Janice A. Fischer, Leroy Hood, Charles F. Aquadro
Publisher: McGraw-Hill Education
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Chapter 19, Problem 18P
Summary Introduction

a.

To determine:

Whether the given proteins in the question act as a proto-oncogene or a tumor-suppressor gene.

Introduction:

The proto-oncogene is a normal gene that promotes cell growth. When a proto-oncogene undergoes a dominant mutation like a gain of function mutation, this gene becomes an oncogene. Tumor-Suppressor genes are normal genes that are responsible for inhibiting the cell proliferation and development of a tumor.

Summary Introduction

b.

To determine:

The effect of the addition of a phosphate group to the phosphatase by kinase A in the given problem.

Introduction:

Phosphatase enzymes are the enzymes responsible for removing phosphates from proteins.

Summary Introduction

c.

To determine:

Whether the phosphatase gene is likely to be a proto-oncogene or a tumor-suppressor gene or neither.

Introduction:

A normal proto-oncogene promotes cell proliferation. A normal tumor-suppressor gene inhibits cell proliferation.

Summary Introduction

d.

To determine:

Whether the listed mutations would lead to excessive cell growth or decreased cell growth if the cell were either homozygous for the mutation, or heterozygous for the mutation and a wild-type allele.

Introduction:

When a tumor suppressor gene undergoes loss of function mutation, it will result in cell proliferation. When a proto-oncogene undergoes gain of function mutation, it will cause cell proliferation. A null mutation makes a gene non-functional.

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Put the following steps for the outline of the growth factor signaling pathway in order: Map Kinase Kinase is Phosphorylated      Proteins involved in gene transcription are activated      Growth factor binds to its receptor in the cytoplasmic membrane    Receptor recruits adaptor protein and GEF    Autophosphorylation of tyrosine residues on the receptor   Structural change of the receptor activates Tyrosine Kinase    Map Kinase Kinase Kinase is phosphorylated   Ras, a small GTPase, is activated by the exchange of GTP for GDP    Map Kinase is Phosphorylated   Map Kinase enters the nucleus
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, has the highest specificity in binding to the target Protein J?
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.
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