Details
- Autor(en) / Beteiligte
- Titel
- The complex of TRIP-Br1 and XIAP ubiquitinates and degrades multiple adenylyl cyclase isoforms
- Ist Teil von
- eLife, 2017-06, Vol.6
- Ort / Verlag
- England: eLife Sciences Publications Ltd
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- EZB Free E-Journals
- Beschreibungen/Notizen
- Adenylyl cyclases (ACs) generate cAMP, a second messenger of utmost importance that regulates a vast array of biological processes in all kingdoms of life. However, almost nothing is known about how AC activity is regulated through protein degradation mediated by ubiquitination or other mechanisms. Here, we show that transcriptional regulator interacting with the PHD-bromodomain 1 (TRIP-Br1, Sertad1), a newly identified protein with poorly characterized functions, acts as an adaptor that bridges the interaction of multiple AC isoforms with X-linked inhibitor of apoptosis protein (XIAP), a RING-domain E3 ubiquitin ligase. XIAP ubiquitinates a highly conserved Lys residue in AC isoforms and thereby accelerates the endocytosis and degradation of multiple AC isoforms in human cell lines and mice. XIAP/TRIP-Br1-mediated degradation of ACs forms part of a negative-feedback loop that controls the homeostasis of cAMP signaling in mice. Our findings reveal a previously unrecognized mechanism for degrading multiple AC isoforms and modulating the homeostasis of cAMP signaling.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2050-084XeISSN: 2050-084XDOI: 10.7554/eLife.28021Titel-ID: cdi_doaj_primary_oai_doaj_org_article_1afc89bd35de4ebc9b1be5e66947c9ee
- Format
- –
- Schlagworte
- adenylyl cyclase, Adenylyl Cyclases - metabolism, Amino acids, Animals, Apoptosis, cAMP, Cell Biology, Cell cycle, Cell Line, Cell lines, Cyclic AMP, degradation, Endocytosis, Homeostasis, Humans, Immunoglobulins, Isoforms, Kinases, Laboratories, Mice, Microscopy, Nuclear Proteins - metabolism, Protein expression, Protein Isoforms - metabolism, Proteins, Proteolysis, Software, Trans-Activators - metabolism, Transcription, TRIP-Br1, Ubiquitin, Ubiquitin-protein ligase, Ubiquitination, X-Linked Inhibitor of Apoptosis Protein - metabolism, XIAP, XIAP protein