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42 Cards in this Set
- Front
- Back
Tertiary structure of Ha-ras has a ______ domain
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CAAX
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RAS has a molecular weight of ____ is ______ in shape and contains (4 secondary structures)
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21K; globular; alpha helices, beta ribbons, loop, and turn regions
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Most human tumors have ___ mutations
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ras
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GTP binding site on the RAS protein located along one face of the protein on a region where oncogenic mutations are observed at which two codons?
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61 and 12
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Codons 61 and 12 are ____ regions.
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turn
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The GTPase activating protein (GAP) binds RAS at _____
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the large AA loop extending from GTP binding site
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In the ____ form RAS binds GTP, in the ______ form RAS binds GDP.
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active; inactive
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RAS inhibitors should have _____ activity
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anti-tumor
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RAS is located on which surface of the plasma membrane
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inner
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RAS responds to signals from the outside by exchanging ____ for _____
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GTP for GDP
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The exchange of GTP for GDP si stimulated by ____ protein
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SOS protein
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SOS protein is activated by
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GRB2
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GRB2 is activated by
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receptor kinase
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When RAS is bound by _____ it activates a downstream ______ cascade that activates transcription factors and genes for growth
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GTP; kinase
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RAS-GTP activity is turned off by intrinsic ______ activity of RAS in concert with extrinsic GAP
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GTPase
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The RAS-GDP structure is inactive in
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signal transduction and promotion of cell division
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The signal transduction pathway begins with
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growth factor binding to a surface receptor
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RAS mutations in codons 12 and 61 short circuit the signal transduction pathway by
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introducing structural changes which inhibit GTPase
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When RAS inhibits GTPase this keeps the protein in which form
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GTP-bound form
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RAS protein must be targeted where to function properly in signal transduction
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inner surface of plasma membrane
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Human carcinomas contain mutations with
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RAS protein
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Drugs to inhibit RAS protein targeting should inhibit
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growth of tumors with RAS mutations (duh)
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RAS is targeted to the cell membrane by a fancy enzyme
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farnesyl transferase
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Farnesyl transferase adds a farnesyl group to
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Cysteine on the C terminal CAAX domain of RAS
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RAS is anchored to the plasma membrane by
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farnesyl lipid group
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This amino acid is targeted the farnesyl group
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cysteine on CAAX domain of RAS
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The tetrapeptide CAAX inhibits which enzyme in vitro
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farnesyl transferase
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What keeps CAAX from inhibiting farnesyl transferase in vivo because
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it is charged and polar, therefore cannot diffuse through the cell membrane
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Hydrophobic benzodiazepine molecule mimics
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the AA dipeptide turn on CAAX motif
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For a CAAX domain to diffuse into a cell it must have the attachment of (2 things) where it can inhibit RAS
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an N terminal Cysteine and C-terminal AA
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Benzodiazepine is a structural relative to
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Valium (yes, please)
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BZA-5B contains an N-terminal _____ and a _____ at the C-terminus
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Cysteine methyl amine; carboxymethyl methionine
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BZA-5B inhibits ______ but not ______
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mutant RAS transformed cells; SRC transformed cells
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RAS mutant transformed cells have
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Specificity
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These code for transcription factors that regulate genes whose products are necessary for cell division and growth
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Nuclear proto-oncogenes
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Signal transduction from a cell-surface event involves
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phosphorylation cascades
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Phosphorylation cascades result in
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stimulation in transcription factor activity and transcription of growth related genes
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Production of transcription factors ___ and ____ is required for cell division
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FOS; JUN
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FOS and JUN factors form a heterodimer termed
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AP-1
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AP-1 functions in
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transcription and activation of growth related genes
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In the _____ form RAS binds GTP
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active
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In the _____ form RAS binds GDP
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inactive
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