N-end rule

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Proteins with destabilizing N-terminal residues such as arginine and leucine are recognized by a RING-type ubiquitin ligase (termed N-recognin or E3-a) that, together with a specific ubiquitin c, mediates poly-ubiquitylation. 

ZnFJJBRl Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway E(MFP) 2(2) 6(6) ... 

Varshavsky, A. The N-end rule functions, mysteries, uses. Proc. Natl Acad. Sci. USA, 1996, 93, 12142-12149. 

Of these, 11 function with ubiquitin and one with each of two different ubiquitin-like (UbL) proteins. Sumo and Nedd8/Rubl [2]. However, while several yeast and metazoan E3s had been identified biochemically by that time, the primary amino acid sequence was known only for a single E3 [7]. This was the Saccharomyces cer-evisiae Ubrlp, which had been studied extensively by Varshavsky and co-workers in delineation of the N-end rule [8, 9]. Its mammalian ortholog, E3a, was the prototypical E3 used in the description of the basics of the ubiquitin pathway by Hershko and Ciechanover [1, 10]. 

Byrd, C., Turner, G. C., and Varshavsky, A. The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor. EMBO J. 1998, 37, 269-77. 

Siepmann, T. j., Bohnsack, R. N., Tokgoz, Z., Baboshina, O., and Haas, A. L. Protein interactions within the N-end rule ubiquitin ligation... 

NEIGHBORING GROUP MEGHANISM ANCHIMERIC ASSISTANCE NEIGHBORING-GROUP PARTIGIPATION INTRAMOLECULAR CATALYSIS SYNARTETIC ACCELERATION N-END RULE... 

NUCLEAR MAGNETIC RESONANCE PROTEIN SYNTHESIS INHIBITORS PROTEIN TURNOVER N-END RULE LEUCINE KINETICS PROTEASE La... 

PULSE-CHASE EXPERIMENTS N-END RULE PULSE RADIOLYSIS PURINE NUCLEOSIDASE PURINE NUCLEOSIDE PHOSPHORYLASE PUTRESCINE CARBAMOYLTRANSEERASE PUTRESCINE N-METHYLTRANSEERASE PUTRESCINE OXIDASE Putrescine synthesis,... 

The mechanistically and functionally complex N-end rule pathway (Fig. 2) is but one of many distinct pathways of the Ub system. The vast functional range of this system stems from the enormous diversity of its physiological substrates. In other words, it is the constitutive or conditional degradation of many specific proteins (cyclins, transcription factors, components of signal transduction pathways, damaged proteins) by ubiquitin-dependent pathways that underlies the involvement of the Ub system in just about every biological circuit in a living cell (5, 6, 9). 

It was recently discovered that 5. cerevisiae Ubrlp and Ufd4p, the E3 components of two distinct Ub-dependent proteolytic pathways, directly interact with specific proteins of the 26S proteasome (1). These results stemmed from the initial finding that overexpression of some subunits of the 19S particle inhibited ubiquitin-dependent degradation of engineered N-end rule substrates. To determine whether this effect could be caused by interaction of these subunits with a component(s) of the N-end rule pathway, glutathione transferase (GST)-pulldown assays with Ubrlp (also called... 

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