Handout 3 - MCB252CellBiology,Spring2008 Handout 03 New...

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MCB 252 Cell Biology, Spring 2008 Handout 03 • How are transcription factors sequestered in the cytoplasm released to enter the nucleus? New Question
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MCB 252 Cell Biology, Spring 2008 Handout 03 Regulates the activity of specific genes TF Nuclear Localization Signal (NLS) hidden NLS exposed NLS Active form TF P Kinase Active form TF P Active form
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MCB 252 Cell Biology, Spring 2008 Handout 03 Regulates the activity of specific genes TF Nuclear Localization Signal active form Inhibitory subunit TF Kinase TF P Kinase
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MCB 252 Cell Biology, Spring 2008 Handout 03 TF TF P TF P Ubiquitin TF Degradation of the inhibitory subunit 1 Destruction box TF P 2
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MCB 252 Cell Biology, Spring 2008 Handout 03 Exterior Cytosol Nucleus NF- k B NLS Inhibitory Unit I-kB kinase Activated TNF receptor E3 ligase polyubiquitin chain degradation of I- k Ba regulation of target genes
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MCB 252 Cell Biology, Spring 2008 Handout 03 • How is a protein poly-ubiquitinated? • How is a poly-ubiquitinated protein degraded? • How does a protein enter the nucleus? More generally, how is the nucleo-cytoplasmic trafficking regulated? New Questions
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MCB 252 Cell Biology, Spring 2008 Handout 03 How is a protein poly-ubiquitinated? Ubiquitin  is a small protein (76 amino acids) that folds up into a compact  globular structure. Ubiquitin functions to regulate protein turnover in a cell by closely regulating protein degradation. Found everywhere. Impacts protein homeostasis.
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MCB 252 Cell Biology, Spring 2008 Handout 03 How is a protein poly-ubiquitinated? Ubiquitin (Ub) is conjugated to a protein through a covalent bond between the glycine at the C-terminal end of Ub and the side chain of a lysine on the protein. protein K Ub Ubiquitinyl-protein is a target for further ubiquitination, the additional ubiquitin units added to the previous ubiquitin to form a ubiquitin chain. Ub Ub Ub Ub Ub Ub Signal for degradation
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MCB 252 Cell Biology, Spring 2008 Handout 03 The conjugation of Ub requires ATP and a three enzyme system , referred to as: E1 Ubiquitin-activating enzyme E2 Ubiquitin-conjugating enzyme E3 Ubiquitin protein ligase • How is a protein poly-ubiquitinated?
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MCB 252 Cell Biology, Spring 2008 Handout 03 • How is a protein poly-ubiquitinated? Ubiquitin is activated at its C-terminal end by E1.
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Handout 3 - MCB252CellBiology,Spring2008 Handout 03 New...

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