dc.contributor.author | Justa-Schuch, Daniela | en_US |
dc.contributor.author | Silva-Garcia, Maria | en_US |
dc.contributor.author | Pilla, Esther | en_US |
dc.contributor.author | Engelke, Michael | en_US |
dc.contributor.author | Kilisch, Markus | en_US |
dc.contributor.author | Lenz, Christof | en_US |
dc.contributor.author | Möller, Ulrike | en_US |
dc.contributor.author | Nakamura, Fumihiko | en_US |
dc.contributor.author | Urlaub, Henning | en_US |
dc.contributor.author | Geiss-Friedlander, Ruth | en_US |
dc.date.accessioned | 2016-11-18T20:05:16Z | |
dc.date.issued | 2016 | en_US |
dc.identifier.citation | Justa-Schuch, Daniela, Maria Silva-Garcia, Esther Pilla, Michael Engelke, Markus Kilisch, Christof Lenz, Ulrike Möller, Fumihiko Nakamura, Henning Urlaub, and Ruth Geiss-Friedlander. 2016. “DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk.” eLife 5 (1): e16370. doi:10.7554/eLife.16370. http://dx.doi.org/10.7554/eLife.16370. | en |
dc.identifier.issn | 2050-084X | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407611 | |
dc.description.abstract | The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a proline or alanine in second position. Although linked to several pathways including cell survival and metabolism, the molecular mechanisms underlying these outcomes are poorly understood. We identified a novel interaction of DPP9 with Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk signalling can be terminated by degradation, requiring the ubiquitin E3 ligase Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in position 1. Pulse-chases combined with mutagenesis studies reveal that Ser1 strongly influences Syk stability. Furthermore, DPP9 silencing reduces Cbl interaction with Syk, suggesting that DPP9 processing is a prerequisite for Syk ubiquitination. Consistently, DPP9 inhibition stabilizes Syk, thereby modulating Syk signalling. Taken together, we demonstrate DPP9 as a negative regulator of Syk and conclude that DPP9 is a novel integral aminopeptidase of the N-end rule pathway. DOI: http://dx.doi.org/10.7554/eLife.16370.001 | en |
dc.language.iso | en_US | en |
dc.publisher | eLife Sciences Publications, Ltd | en |
dc.relation.isversionof | doi:10.7554/eLife.16370 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039030/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Syk | en |
dc.subject | DPP9 | en |
dc.subject | N-end rule | en |
dc.subject | protein half-life | en |
dc.subject | Cbl | en |
dc.subject | B cell signalling | en |
dc.subject | Human | en |
dc.title | DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | eLife | en |
dc.date.available | 2016-11-18T20:05:16Z | |
dc.identifier.doi | 10.7554/eLife.16370 | * |