Epitopes described in "Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies."

Article Authors:Kim Newton; Marissa L Matsumoto; Ingrid E Wertz; Donald S Kirkpatrick; Jennie R Lill; Jenille Tan; Debra Dugger; Nathaniel Gordon; Sachdev S Sidhu; Frederic A Fellouse; Laszlo Komuves; Dorothy M French; Ronald E Ferrando; Cynthia Lam; Deanne Compaan; Christine Yu; Ivan Bosanac; Sarah G Hymowitz; Robert F Kelley; Vishva M Dixit
Article Title:Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies.
Reference Detail
Reference ID:1019698
Abstract:Posttranslational modification of proteins with polyubiquitin occurs in diverse signaling pathways and is tightly regulated to ensure cellular homeostasis. Studies employing ubiquitin mutants suggest that the fate of polyubiquitinated proteins is determined by which lysine within ubiquitin is linked to the C terminus of an adjacent ubiquitin. We have developed linkage-specific antibodies that recognize polyubiquitin chains joined through lysine 63 (K63) or 48 (K48). A cocrystal structure of an anti-K63 linkage Fab bound to K63-linked diubiquitin provides insight into the molecular basis for specificity. We use these antibodies to demonstrate that RIP1, which is essential for tumor necrosis factor-induced NF-kappaB activation, and IRAK1, which participates in signaling by interleukin-1beta and Toll-like receptors, both undergo polyubiquitin editing in stimulated cells. Both kinase adaptors initially acquire K63-linked polyubiquitin, while at later times K48-linked polyubiquitin targets them for proteasomal degradation. Polyubiquitin editing may therefore be a general mechanism for attenuating innate immune signaling.
Affiliations:Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Reference Type:Literature
PubMed ID:18724939
Journal Volume:134
Article Pages:668-78
Journal ISSN:1097-4172
Article Chemical List:Antibodies;Nuclear Pore Complex Proteins;Peptide Library;RNA-Binding Proteins;Ubiquitin;Interleukin-1 Receptor-Associated Kinases
Article MeSH List:Animals; Antibodies(metabolism); Cell Line; Humans; Interleukin-1 Receptor-Associated Kinases(metabolism); Mass Spectrometry; Mice; Mice, Inbred C57BL; Nuclear Pore Complex Proteins(chemistry; metabolism); Peptide Library; RNA-Binding Proteins(chemistry; metabolism); Saccharomyces cerevisiae; Schizosaccharomyces; Ubiquitin(chemistry; metabolism); Ubiquitination
Curation Last Updated:2014-10-03 22:06:15