Networking at the Protein Society Symposium

TY - JOUR

T1 - Networking at the Protein Society Symposium

AU - McKnight, C. James

AU - Cordes, Matthew H.J.

N1 - Funding Information: The discovery that cellular processes can be regulated by spatially and temporally controlled protein degradation, independent of transcription and translation, has added a new dimension to our understanding of cellular regulation. The Stein and Moore Award, sponsored by the Merck Foundation, was presented to Avram Hershko (Technion–Israel Institute of Technology) and Alexander Varshavsky (California Institute of Technology) for their complementary roles in elucidating the ubiquitin system and its crucial biological functions. Hershko presented a retrospective of his laboratory’s groundbreaking work in discovering the ubiquitin system, including the E1, E2 and E3 enzymes responsible for ubiquitin conjugation12. Varshavsky focused on recent advances in unlocking the mechanisms and functions of the ubiquitin-dependent N-end rule pathway. The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue13. Known functions of the N-end rule pathway include control of peptide import, regulation of apoptosis, chromosome segregation, regulation of meiosis, cardiovascular development and leaf senescence in plants. Ubiquitin ligases of the N-end rule pathway recognize degradation signals (degrons) that include the signals called N-degrons. An N-degron consists of a protein’s destabilizing N-terminal residue and an internal lysine residue. The latter is the site of formation of a polyubiquitin chain, recognized by the 26S proteasome, a large multisubunit protease. The N-end rule has a hierarchic structure. N-terminal asparagine and glutamine are tertiary destabilizing residues in that they function through their deamidation, by N-terminal amidohydrolases, to yield the secondary destabilizing residues aspartic acid and glutamic acid. The activity of N-terminal aspartic acid and glutamic acid (and cysteine in multicellular eukaryotes) requires their conjugation, by arginyltransferase, to arginine, one of the primary destabilizing residues.Varshavsky also described recent studies revealing new functions of the N-end rule pathway14. Over the

PY - 2005/10

Y1 - 2005/10

UR - http://www.scopus.com/inward/record.url?scp=33644816494&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644816494&partnerID=8YFLogxK

U2 - 10.1038/nchembio1005-239

DO - 10.1038/nchembio1005-239

M3 - Letter

C2 - 16408046

AN - SCOPUS:33644816494

SN - 1552-4450

VL - 1

SP - 239

EP - 242

JO - Nature chemical biology

JF - Nature chemical biology

IS - 5

ER -