Concept explainers
Because of its accessibility and biological significance, the proteome of human plasma has been intensively studied and used co provide biomarkers for such conditions as myocardial infarction (troponin) and congestive heart failure (B-type natriuretic peptide). Polanski and Anderson compiled a lise of 1261 proteins, some occurring in plasma, that appear to be differentially expressed in human cancers [Polanski, M., and Anderson, N. L. (2006) Biomarker Insights 2:1–48]. Of these 1261 proteins, only 9 have been recognized by the FDA as tumor-associated proteins. First, what advantage should there be in using plasma as a diagnostic screen for cancer? Second, what criteria should be used to validate that a cancerous state can be assessed through the plasma proteome?
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EBK CONCEPTS OF GENETICS
- Cancer can be defined as an abnormal proliferation of cells that defy the normal regulatory controls observed by normal cells. Recently, histone deacetylation therapies have been attempted in the treatment of certain cancers [reviewed by Delcuve et al. (2009)]. Specifically, the FDA has approved histone deacetylation (HDAC) inhibitors for the treatment of cutaneous T-cell lymphoma. Explain why histone acetylation might be associated with cancer and what the rationale is for the use of HDAC inhibitors in the treatment of certain forms of cancer.arrow_forwardWhich phenomenon is not readily explained by the 'induced-fit' hypothesis, that is readily explained by the 'fluctuation-fit hypothesis? Catalysis by optimal interaction with the transition state of substrates. O Specificity of enzymes for substrates. O Lower binding affinity for products, enabling their release once chemistry has happened. O Cooperativity of binding to the remaining 3 sites of hemoglobin when oxygen binds to the first of the four sites.arrow_forwardA pharmaceutical company developed a drug, CP788, that inhibits the interaction of Grb2 with SH2 domains as a treatment for breast cancer. As the data below shows, the compound inhibits activation of RAS in MDA-MB-468 breast cancer cells (Figure A) and anchorage-dependent growth (Figure B solid line) in MDA-MB-468 breast cancer cells. Note that these experimets were done in the presence of EGF. Briefly explain the steps in the pathway by which inhibition of Grb2/SH2 interaction would inhibit activation of RAS (limit 5-6 sentences). A Inhibition of RAS Activation by CP788 % RAS Activation 120 100 80 60 20 0 0 50 [CP788] UM 100 B Colonies number (% of untreated control) 120 100 80 60 40 20 0 10-² HigHt 10-¹ 10⁰ 10¹ 10² 10³ [CP788] UMarrow_forward
- Briefly describe the following properties of the Rab and Arf GTPases: a) Size, structure and cellular localization (for structure I want to know if they are lipidated and any other unique features) , b) How are they activated and inactivated (i.e. include the GEFs and GAPs), c). Give an example of downstream cellular effects.arrow_forwardWilms tumor 1, or nephroblastoma, is caused by mutations in the WT1 gene, which encodes a transcription factor. You have identified a novel variant in WT1: Arg422Pro. You have control cells and cells that have been engineered to carry the homozygous WT1 p.Arg422Pro mutation. You want to assess effects of this mutation on a variety of endpoints. For each endpoint listed below, choose the one technique is best suited to answer the question. Choose from: array CGH, qRT-PCR, qPCR, RNA-seq, FISH, in situ hybridization, western blot, immunostaining, WT1 ChIP-seq, WT1 ChIP-PCR, ATAC-seq, 3C Endpoint Technique? WT1 protein amount (quantitative) Western blot WT1 protein binding to all enhancers, genome-wide Chip-seq WT1 mRNA amount (quantitative) WT1 protein subcellular localization Quantitative assessment of all mRNAs in these cells (genome-wide) RNAseq Chromatin interactions between a specific WT1 chromatin binding site (identified above)…arrow_forwardExplain the signifi cance of the observation that peptides such as fMet-Leu-Phe “activate” the phagocytotic (particle-engulfi ng) functions of mammalian leukocytes (white blood cells).arrow_forward
- Proteins that are retained in the ER have a KDEL sequence at their C-terminus. To test the idea that KDEL is both necessary and sufficient for retention in the ER, two experiments were performed. First, it was deleted from protein disulfide isomerase (PDI), and this form of PDI got secreted. Second, it was attached to a peptide growth hormone, which is normally secreted from the cell. This modified peptide still got secreted. Which interpretation does this support? The data do not allow for an interpretation, additional experiments are needed. KDEL is sufficient but not necessary for ER retention. KDEL is both necessary and sufficient for ER retention. KDEL is necessary but not sufficient for ER retention.arrow_forwardTroponin is a complex composed of Troponin C (TnC), Troponin I (TnI), and Troponin T (TnT); the complex is found in skeletal and cardiac muscle, but not smooth muscle. Two "isoforms" of TnI and two "isoforms" of TnT are expressed in human skeletal muscle tissue. Q:The isoforms of TnI in the sentence above mean: A:One single TnI gene encodes two different TnI proteins as a result of alternative splicing of the TnI pre-mRNA. B:There are two different TnI genes, each produces a TnI protein.arrow_forwardThe following diagram is from a paper investigating the role of β4 integrin in breast cancer. They examined the expression of miRNAs (rows) in ten β4 positive and ten β4 negative breast cancers. Each array was performed in triplicate (columns) (Gerson, 2012). A. Describe how you think this array was carried out. B. β4 integrin is normally involved in attaching epithelial cells to the extracellular matrix and holding them in place, but in cancer, it can be involved in attaching cells to actin and increasing motility as well as in cell signaling. How is β-integrin expression related to miRNA expression? What do you think this means for these breast cancers?arrow_forward
- The steroid progesterone has an important role in the female reproductive system. Researchers interested in studying membrane progestin receptors (MPRS) developed a method to produce and purify the protein in active form. First, the researchers devised a way to prepare a specific MPR known as hMPRA using the machinery of yeast cells. In order to facilitate purification and identification in later studies, they manipulated the yeast cells so that they attached two different tags to the C-terminal end of the protein. The first tag, Compound 1, is a peptide sequence that acts as an epitope, part of a much larger peptide sequence that is recognized by the immune system. The second sequence consisted of six consecutive histidine residues (His). This sequence binds tightly to Ni2+ cations. In chromatography, (His), tag labeled proteins can be eluted from Ni²+. supported columns by adding a small molecule to the eluent that mimics the side chain of histidine.…arrow_forwardThe steroid progesterone has an important role in the female reproductive system. Researchers interested in studying membrane progestin receptors (MPRs) developed a method to produce and purify the protein in active form. First, the researchers devised a way to prepare a specific MPR known as hMPRA using the machinery of yeast cells. In order to facilitate purification and identification in later studies, they manipulated the yeast cells so that they attached two different tags to the C-terminal end of the protein. The first tag, Compound 1, is a peptide sequence that acts as an epitope, part of a much larger peptide sequence that is recognized by the immune system. The second sequence consisted of six consecutive histidine residues (His). This sequence binds tightly to Ni2+ cations. In chromatography, (His), tag labeled proteins can be eluted from Ni²+- supported columns by adding a small molecule to the eluent that mimics the side chain of histidine. After preparing hMPRA, the…arrow_forwardThis is the full question.. "Both the cytokinin receptor encoded by CRE1 and the ethylene receptor encoded by ETR1 are examples of" Both the cytokinin receptor encoded by CRE1 and the ethylene receptor encoded by ETR1 are examples of O Leucine-rich repeat receptor kinase • The response regulator component of a two-component sensor histidine kinase (i.e., the component that directly activates transcription (type B ARRS, in the case of cytokinin) or directly mediates a response (type A ARRS)) O Regulatory molecules that bind calcium O The sensor histidine kinase component of a two-component sensor histidine kinase (i.e., the part that receives the signal and passes it to other components of the signal transduction cascade) O Proteins that shuttle from the cytoplasm to the nucleus to alter gene expressionarrow_forward
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