LECTURE 17 - REGULATED PROTEOLYSIS

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10 Terms

1
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what are latent gene regulatory proteins

proteins which only enter the nucleus to regulate gene expression after being instructed to do so, and are otherwise maintained in the cytoplasm

2
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what is regulated proteolysis used for

control activity and location of regulatory proteins

3
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what is NF-kB stand for

nuclear factor kappa beta

4
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what does binding of IkB to NF-kB do

it occludes the NF-kB NLS (nuclear localisation signal) in non-stimulated cells

5
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explain the pathway of NF-kB

  • NF-kB binds to IkB

  • TNF binds to TNF receptor, and transmits signal to IKK, activating it

  • IKK phsophorylates IkB, IkB is ubiquitylated and degraded by proteosome

  • NF-kB then exposed, and can translocate into nucleus where it induced transcription of inflammatory response genes; inflammatory cytokines


6
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what is Wnt signalling involved in

embryogenesis, cell polarity, cell migration and cell fate

7
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explain the Wnt signalling pathway

  • free beta catenin in cytoplasm is degraded in non stimulated cells

  • beta catenin associates with destruction complex comprised of APC, Axin, GSK-beta 3 and CKI

  • GSK-beta3 and CKI phosphorylate beta catenin, and this signals polyubiquitination and degradation by proteosome

  • bidning of Wnt to frizzled receptor and LRP results in binding of dishevelled to frizzled

  • dishevelled recruits destruction complex, beta catenin no longer associates with destruction complex

  • beta catenin translocates into the nucleus to enable gene expression of early cell cycle genes


8
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describe lateral inhibition of notch signalling

when a precursor cell commits to becoming a particular lineage, it signals to prevent its surrounding cells from becoming the same

9
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what are the 3 proteolytic cleavage events that regulate Notch activity

  1. site 1 cleavage in the golgi for receptor maturation

  2. site 2 cleavage by ADAM for ectodomain shedding

  3. site 3 cleavage by gamma secretase to release notch intracellular domain (NICD)


10
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explain notch signalling after the 3 cleavage events

  • NICD translocates into the nucleus and binds to CSL

  • Notch to CSL binding switches CSL from transcriptional repressor to transcriptional activator

  • Notch activation is not reversible