title: The N-end rule pathway: from recognition by N-recognins, to destruction by AAA+proteases.
abstract: Intracellular proteolysis is a tightly regulated process responsible for the targeted removal of unwanted or damaged proteins. The non-lysosomal removal of these proteins is performed by processive enzymes, which belong to the AAA+superfamily, such as the 26S proteasome and Clp proteases. One important protein degradation pathway, that is common to both prokaryotes and eukaryotes, is the N-end rule. In this pathway, proteins bearing a destabilizing amino acid residue at their N-terminus are degraded either by the ClpAP protease in bacteria, such as Escherichia coli or by the ubiquitin proteasome system in the eukaryotic cytoplasm. A suite of enzymes and other molecular components are also required for the successful generation, recognition and delivery of N-end rule substrates to their cognate proteases. In this review we examine the similarities and differences in the N-end rule pathway of bacterial and eukaryotic systems, focusing on the molecular determinants of this pathway.
authors.affiliation: Department of Biochemistry, L Trobe Institute for Molecular Science, La Trobe University, Melbourne, 3086, Australia. d.dougan@latrobe.edu.au
authors.forename: D A
authors.initials: DA
authors.lastname: Dougan
authors.forename: D
authors.initials: D
authors.lastname: Micevski
authors.forename: K N
authors.initials: KN
authors.lastname: Truscott
mesh_terms: D049069:ATP-Dependent Proteases / Q000737:chemistry*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006801:Humans; D053858:Metabolic Networks and Pathways; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry
chemical_list: D043743:Ubiquitin-Protein Ligase Complexes; D049069:ATP-Dependent Proteases; D046988:Proteasome Endopeptidase Complex