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24 Cards in this Set
- Front
- Back
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What happens during cell recruitment
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most cells are not cycling
-to get from G0 to G1, you need a stimulus and genes - immediate early genes, delayed early genes, late genes -induced cell proliferation involves: -initiated by growth factors -requires cell adhesion/anchorage -is accompanied by an orderly expression of certain defined gene sets -culminates in DNA synthesis and cell division |
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Growth gene expression
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-is temporally controlled throughout the cell cycle
-sequentially activated for a specific duration dependent on the stimulus -length of activation depends onthe stimulus |
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What are the types of immediate early genes & what do they do?
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1. mostly transcription factors
regulate genes involved in metabolic activities to culmintate in DNA synthesis 2. ADHESION FACTORS have to be anchor dependent to grow, |
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Name examples of early intermediate genes and what type they are
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c-MYC - HLH (helix loop helix domain)
c-fos - leucine zipper c-jun -leucine zipper |
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dyad symmetry motif
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- motif needed for homodimerization fo immediate early Tx factors
-for instance Max-Max homodimer will bind a dyad symmetry motif |
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asymmetric motif
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-required for immediate early gene Tx factor heterodimerization -
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What are the two most important things to remember about tx factors - immediate early response genes
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1. they work in PAIRS - homodimers and heterodimers
2. the N terminal region (the DNA binding domain is very important - its really stiff so that it can intercalcate into the DNA, and then there's a really important arginine that breaks the helix to give the stiff structure some flexibility |
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E-box
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- a sequence on the DNA that the Tx factors recognize through their DBD
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How is regulation of gene expression wtih Tx factors economical?
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-because tx factors homodimerize (need dyad motif) and heterodimerize (need asymmetric motif)- this means yo can get a lot of different results with very few protein types
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What are the parts of c-MYC?
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- a TAD - a transcriptional activating domain - (not found in MAX)
-HLH - helix loop Helix -fascilitates DNA binding -ZIP - region where Tx factor dimerizes with another Tx factor -NLS to tell it to go to the nucleus |
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What are the parts of MAX
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-no TAD, that's why Max-Max homodimers cannot activate Tx
-HLH - for DNA binding -ZIP region for dimerization -very small truncated protein |
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Who has HLH?
Who has Leucine zippers? |
- c-Myc and Max have HLC
-c-jun & c-fos have leucine zippers |
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Why can't Max-Max homodimer activate Tx?
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Max doesn't have a TAD domain, it needs c-MYC to activate Tx
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Some examples of genes tat have E boxes?
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Thymidylate Kinase (nucleotide synthesis)
Dihydrofolate reductase Ornithine decarboxylase Plasminogen activating factor |
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When is c-MYC activated constituitively?
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-in diseased states like
-Burkitt's lymphoma (chromosomal rearrangement) -cancer (breast cancer and small cell lung carcinoma) -sporadic cancers |
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what are three mechanisms whereby c-MYC can be constituitively activated?
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-chromosomal rearangement (Burkitts)
-gene amplification (breast carcinoma & SCL carsinoma) -stimulated expression (sporadic cancer) |
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Burkitts lymphoma
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-chromosomal translocation results in overproduction of c-MYC which results in cancer
-chromosome 8 & 14 |
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importance of c-MYC
how does it regulate, what does it regulate? |
-TX factor that helps move cells out of G0 and into G1 so that proliferation can occur
-regulates lots of target genes through a hex a nucleotide motif (E-box) CACGTG -regulates cell growth, proliferation, angiogenesis |
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hex a nucleotide motif (E-box) CACGTG
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-c-MYC regulates lots of target genes through a hex a nucleotide motif (E-box) CACGTG
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3 basic properties of HLH and Leucine zipper Tx factor family members
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- function as homodimers and heterodimers
-regulate gene expression in a combinatorial manner -are sequence specific DNA binding proteins |
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activated c-MYC state
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PHOSPHORYLATED c-mYC
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Some key differences between MAX-MAx and MAX-Myc
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- homodimers MAX are very stable,
-heterodimers MAx-Myc are unstable - so that they get ubiquinitated and degraded eventually, the homeostatic balance favors repression (MAX-MAX) |
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Binding of MAX-MYC heterodimer
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-causes activation of Tx
-histone acetylation -DNA demethylation |
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Understanding cell growth control is critical to our perception of
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-normal development
-wound healing -diseases which are clinical problems |
