Molecular Biochemistry II

Protein Degradation

Reading:

Textbook Reading: Voet & Voet, Biochemistry, 3rd Edition, p. 515-528, 1352-1365.

Some recent articles (optional reading): 
A. Glading, D. A. Lauffenburger & A. Wells (2002) "Cutting to the chase: calpain proteases in cell motility," Trends in Cell Biol. 12: 46-54.
E. N. Shiozaki & Y. Shi (2004) "Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology," Trends in Biochem. Sci. 39: 486-494.
H. Hlzl, B. Kapelari, J. Kellermann, E. Seemller, M. Smegi, A. Udvardy, O. Medalia, J. Sperling, S. A Mller, A. Engel & W. Baumeister (2000) "The regulatory complex of Drosophila melanogaster 26S proteasomes: subunit composition and localization of a deubiquitylating enzyme," J. Cell Biol. 150: 119-129.
F. G. Whitby, E. I. Masters, L. Kramer, J. R. Knowlton, Y. Yao, C. C. Wang & C. P. Hill (2000) "Structural basis for the activation of 20S proteasomes by 11S regulators," Nature 408: 115-120.
F. Kopp, B. Dahlmann & L. Kuehn (2001) "Reconstitution of hybrid proteasomes from purified PA700-20S complexes and PA28ab activator: Ultrastructure and peptidase activities," J. Mol. Biol. 313: 465-471.
M. Groll & T. Clausen (2003) "Molecular shredders: how proteasomes fulfill their roll," Current Opinion in Struct. Biol. 13: 665-673.
M. Orlowski & S. Wilk (2003) "Ubiquitin-independent proteolytic functions of the proteasome," Arch. Biochem. Biophys. 415: 1-5.
A. M. Cuervo (2004) "Autophagy: in sickness and in health," Trends in Cell Biol. 14: 70-77.
N. E. Zachara & G. W. Hart (2004) "O-GlcNAc modification: a nutritional sensor that modulates proteasome function," Trends in Cell Biol. 14: 218-221.
A. Weihofen & B. Martoglio (2003) "Intramembrane-cleaving proteases: controlled liberation of proteins and bioactive peptides," Trends in Cell Biol. 13: 71-78.
N. Wei & X. W.  Deng (2003) "The COP9 signalosome," Annu. Rev. Cell Dev. Biol. 19: 261-286.
P. A. Robinson & H. C. Ardley (2004) "Ubiquitin-protein ligases," J. Cell Sci. 117: 5191-5194.
J. C. Whisstock, S. P. Bottomley, P. I. Bird, R. N. Pike & P. Coughlin (2005) "Serpins 2005 - fun between the b-sheets," FEBS J. 272: 4868-4873.
D. J. Klionsky (2005) "The molecular machinery of autophagy: unanswered questions," J. Cell Sci. 118: 7-18.
U. Nair & D. J. Klionsky (2005) "Molecular mechanisms and regulation of specific and nonspecific autophagy pathways in yeast," J. Biol. Chem. 280: 41785-41788.
P. Ho & C. J. Hawkins (2005) "Mammalian initiator apoptotic caspases," FEBS J. 272: 5436-5453.
C. Adrain, G. Brumatti & S. J. Martin (2006) "Apoptosomes: protease activation platforms to die from," Trends in Biochem. Sci. 31: 243-247.
J. A. Huntington (2006) "Shape-shifting serpins - advantages of a mobile mechanism," TRENDS in Biochem. Sci. 31: 427-435.
S. Kaushik & A. M. Cuervo (2006) "Autophagy as a cell-repair mechanism: activation of chaperone-mediated autophagy during oxidative stress," Molec. Aspects of Med. 27: 444-454.
A. von Mikecz (2006) "The nuclear ubiquitin-proteasome system," J. Cell Sci. 119: 1977-1984.
D. M. Smith, N. Benaroudj & A. Goldberg (2006) "Proteasomes and their associated ATPases: A destructive combination," J. Struct. Biol. 156: 72-83.
B. Turk & V. Stoka (2007) "Protease signalling in cell death: caspases versus cysteine cathepsins," FEBS Lett. 581: 2761-2767.
C. Naujokat, D. Fuchs & C. Berges (2007) "Adaptive modification and flexibility of the proteasome system in response to proteasome inhibition," Biochim. Biophys. Acta 1773: 1389-1397.

Potential Test Question:

1. a. Summarize how proteins are tagged for degradation by proteasomes. Include the roles of E1, E2, and E3 in this process. Which of these proteins is responsible for specificity, in determining which proteins are tagged for degradation?
b. Describe the structure and subunit composition of the eukaryotic 20S proteasome core complex. What is its function? Where are catalytic domains located? What is the essential residue in each of these catalytic domains? 
c. What activities are exhibited by different parts of the 19S regulatory cap complex? What are thought to be their roles?

Copyright 1998-2008 by Joyce J. Diwan. All rights reserved.

Lecture Notes on
Protein Degradation

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Protein Degradation  

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