title: [The protein-destroying machinery].
abstract: Proteolysis plays an essential role in the regulation of divergent cellular activities by catalyzing biological reactions rapidly, in an orderly manner, exhaustively, and uni-directionally. It is now clear that intracellular proteolysis actively controls various biologically important processes, such as cell-cycle control, DNA repair, immune and stress responses, and protein quality-control. Recently, it has been clarified, as a central scenario, that dysfunctioning of proteolysis, which plays a central role in the clearance of impaired proteins by facilitating proteolytic removal of improperly-folded proteins or unfolded proteins to maintain normal cell functions, causes various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, poly-glutamine diseases, amyotrophic lateral sclerosis, and prion disease, which are increasing in the aging society of the 21st century. The degradation machinery in eukaryotic cells can be divided into two distinct sub-pathways, i.e. , the ubiquitin(a posttranslational modifier serving as the degradation signal)-proteasome(a eukaryotic ATP-dependent protease)system and the autophagy(Greek for self-eating)-lysosome system. Emerging evidence emphasizes the importance of both proteolytic pathways in various biological and pathological processes, such as cellular remodelling, tumorigenesis and developmental programmes. Proteolysis may contribute to the development of a new bio-science field as well as to that of therapies for the aforementioned intractable diseases.
authors.affiliation: The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D001343:Autophagy; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins; D046988:Proteasome Endopeptidase Complex