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TRIP-Br1 Mediates Degradation of Multiple Adenylyl Cyclase Isoforms by XIAP E3 Ligase
Başlık:
TRIP-Br1 Mediates Degradation of Multiple Adenylyl Cyclase Isoforms by XIAP E3 Ligase
Yazar:
Hu, Wenbao, author.
ISBN:
9780438130654
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (106 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Pingbo Huang.
Özet:
Adenylyl cyclases (ACs) catalyze conversion of ATP to 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 TRIP-Br1 (Transcriptional Regulator Interacting with the PHD-Bromodomain 1), a newly identified protein with poorly characterized functions, modulates degradation of multiple AC isoforms. TRIP-Br1 acts as an adaptor that bridges the interaction of multiple AC isoforms with XIAP (X-linked inhibitor of apoptosis). XIAP is also a RING-domain E3 ubiquitin ligase of multiple signaling proteins. SERTA domain of TRIP-Br1 binds C1b domains of multiple AC isoforms. The N-terminus of TRIP-Br1 binds BIR2 domain of XIAP, thus recruiting XIAP to ACs, and thereby ubiquitinate ACs. Overexpressing both TRIP-Br1 and XIAP reduced ACs expression and increased their ubiquitination. Knocking down either TRIP-Br1 or XIAP suppressed AC ubiquitination. XIAP ubiquitinates a highly conserved Lys residue in AC isoforms and thereby accelerates the endocytosis and degradation of multiple AC isoforms. Our findings reveal a previously unrecognized mechanism for degrading multiple AC isoforms and modulating cAMP signaling and identify an unexpected link between cAMP signaling and other signaling pathways associated with TRIP-Br1 and XIAP.
Notlar:
School code: 1223
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(696764.1) | 696764-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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