Ligand of Numb proteins LNX1p80 and LNX2 interact with the human glycoprotein CD8a and promote its ubiquitylation and endocytosis
نویسندگان
چکیده
Massimo D’Agostino, Giusy Tornillo, Maria Gabriella Caporaso, Maria Vittoria Barone, Eric Ghigo, Stefano Bonatti* and Giovanna Mottola* Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples ‘Federico II’, Via S. Pansini 5, 80131 Naples, Italy Dipartimento di Pediatria, European Laboratory For the Investigation of Food Induced Disease, University of Naples ‘Federico II’, Via S. Pansini 5, 80131 Naples, Italy URMITE, CNRS UMR6236-IRD 3R198, Université de la Méditerranée, 27 Bd Jean Moulin 13358 Marseille CEDEX 05, France
منابع مشابه
Ligand of Numb proteins LNX1p80 and LNX2 interact with the human glycoprotein CD8α and promote its ubiquitylation and endocytosis.
E3 ubiquitin ligases give specificity to the ubiquitylation process by selectively binding substrates. Recently, their function has emerged as a crucial modulator of T-cell tolerance and immunity. However, substrates, partners and mechanism of action for most E3 ligases remain largely unknown. In this study, we identified the human T-cell co-receptor CD8 α-chain as binding partner of the ligand...
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The structural continuity of tight junctions (TJs) is consistently maintained even when epithelial cells divide and move within the cellular sheet. This process is associated with dynamic remodeling of TJs by coordinated internalization and generation of claudin-based TJ strands, but the molecular mechanism behind the regulated turnover of TJs remains largely unknown. In this study, we identifi...
متن کاملProteomic analysis reveals novel ligands and substrates for LNX1 E3 ubiquitin ligase
Ligand of Numb protein X1 (LNX1) is an E3 ubiquitin ligase that contains a catalytic RING (Really Interesting New Gene) domain and four PDZ (PSD-95, DlgA, ZO-1) domains. LNX1 can ubiquitinate Numb, as well as a number of other ligands. However, the physiological relevance of these interactions in vivo remain unclear. To gain functional insights into the LNX family, we have characterised the LNX...
متن کاملStructural basis for the indispensable role of a unique zinc finger motif in LNX2 ubiquitination.
LNX (Ligand of Numb Protein-X) proteins, LNX1 and LNX2, are RING- and PDZ-based E3-ubiquitin ligases known to interact with Numb. Silencing of LNX2 has been reported to down-regulate WNT and NOTCH, two key signaling pathways in tumorigenesis. Here we report the identification of the domain boundary of LNX2 to confer its ubiquitination activity, its crystal structure along with functional studie...
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OBJECTIVE Vascular endothelial growth factor (VEGF) signaling is a major regulator of physiological and pathological angiogenesis. VEGF receptor activity is strongly controlled by endocytosis, which can terminate or enhance signal transduction in the angiogenic endothelium, but the exact molecular regulation of these processes remains incompletely understood. We have therefore examined the func...
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