Description This volume brings together a set of reviews that provide a summary of our current knowledge of the proteolytic machinery and of the pathways
of protein breakdown of prokaryotic and eukaryotic cells. Intracellular protein degradation is much more than just a mechanism for the
removal of incorrectly folded or damaged proteins. Since many short-lived proteins have important regulatory functions, proteolysis makes
a significant contribution to many cellular processes including cell cycle regulation and transciptional control. In addition, limited
proteolytic cleavage can provide a rapid and efficient mechanism of enzyme activation or inactivation in eukaryotic cells.
In the
first chapter, Maurizi provides an introduction to intracellular protein degradation, describes the structure and functions of bacterial
ATP-dependent proteases, and explores the relationship between chaperone functions and protein degradation. Many of the principles also
apply to eukaryotic cells, although the proteases involved are often not the same. Interestingly, homologues of one of the bacterial
proteases, Ion protease, have been found in mitochondria in yeast and mammals, and homologues of proteasomes, which are found in all
eukaryotic cells (see below), have been discovered in some eubacteria.
Studies of proteolysis in yeast have contributed greatly
to the elucidation of both lysosomal (vacuolar) and nonlysosomal proteolytic pathways in eukaryotic cells. Thumm and Wolf (chapter 2)
describe studies that have elucidated the functions of proteasomes in nonlysosomal proteolysis and the contributions of lysosomal proteases
to intracellular protein breakdown. Proteins can be selected for degradation by a variety of differen mechanisms. The ubiquitin system
is one complex and highly regulated mechanism by which eukaryotic proteins are targetted for degradation by proteosomes. In chapter 3,
Wilkinson reviews the components and functions of the ubiquitin system and considers some of the known substrates for this pathway which
include cell cycle and transcriptional regulators.
The structure and functions of proteosomes and their regulatory components are
described in the two subsequent chapters by Tanaka and Tanahashi and by Dubiel and Rechsteiner. Proteasomes were the first known example
of threonine proteases. They are multisubunit complexes that, in addition to being responsible for the turnover of most short-lived nuclear
and cytoplasmic protein, are also involved in antigen processing for presentation by the MHC class I pathway. Recent studies reviewed
by McCracken and colleagues (chapter 6) lead to the exciting conclusion that some ER-associated proteins are degraded by cytosolic proteasomes.
Lysosomes are responsible for the degradation of long-lived proteins and for the enhanced protein degradation observed under starvation
conditions. In chapter 7 Knecht and colleagues review the lysosomal proteases and describe studies of the roles of lysosomes and the
mechanisms for protein uptake into lysosomes. Methods of measuring the relative contribution of different proteolytic systems (e.g.,
ubiquitin-proteasome pathway, calcium-dependent proteases, lysosomes) to muscle protein degradation, and the conclusions from such studies,
are reviewed by Attai and Taillinder in the following chapter.
Finally, proteases play an important role in signaling apoptosis
by catalyzing the limited cleavage of enzymes. Mason and Beyette review the role of the major players, caspases, which are both activated
by and catalyze limite proteolysis, and also consider the involvement of other protoelytic enzymes in this pathway leading cell death.
Contents Contents. List of Contributors. Preface (A.J. Rivett). Biochemical Properties and Biological Functions of ATP-Dependent Proteases in Bacterial
Cells (M.R. Maurizi). From Proteasome to Lysosome: Studies on Yeast Demonstrate the Principles of Protein Degradation in the Eukaryote
Cell (M. Thumm and D.H. Wolf). Cellular Regulation by Ubiquitin-Dependent Processes (K.D. Wilkinson). The 20s Proteasome: Subunits and
Functions (K. Tanaka and N. Tanahashi). The 19s Regulatory Complex of the 26s Proteasome (W. Dubiel and M. Rechsteiner). Endoplasmic
Reticulum0Associated Protein Degradation: an Unconventional Route to a Familiar Fate (A.A. McCracke, E.D. Werner, and J.L. Brodsky).
Pathways for the Degradation of Intracellular Proteins within Lysosomes in Higher Eukaryotes (E. Knecht, J.J.M. de Llano, E.J. Andreu,
and I.M. Miralles). The Critical Role of the Ubiquitin-proteasome Pathway in Muscle Wasting in Comparison to Lysosomal and Ca2+-dependent
Systems (D. Attaix and D. Taillandier). Proteolysis in Apoptosis: Enzymes and Substrates (G.G.F. Mason, and J. Beyette). Index.
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