دورية أكاديمية
Structural basis and specificity of human otubain 1-mediated deubiquitination
| العنوان: | Structural basis and specificity of human otubain 1-mediated deubiquitination |
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| المؤلفون: | Edelmann, Mariola J., Iphöfer, Alexander, Akutsu, Masato, Altun, Mikael, di Gleria, Katalin, Kramer, Holger B., Fiebiger, Edda, Dhe-Paganon, Sirano, Kessler, Benedikt M. |
| المصدر: | Biochemical Journal ; volume 418, issue 2, page 379-390 ; ISSN 0264-6021 1470-8728 |
| بيانات النشر: | Portland Press Ltd. |
| سنة النشر: | 2009 |
| الوصف: | OTUB (otubain) 1 is a human deubiquitinating enzyme that is implicated in mediating lymphocyte antigen responsiveness, but whose molecular function is generally not well defined. A structural analysis of OTUB1 shows differences in accessibility to the active site and in surface properties of the substrate-binding regions when compared with its close homologue, OTUB2, suggesting variations in regulatory mechanisms and substrate specificity. Biochemical analysis reveals that OTUB1 has a preference for cleaving Lys48-linked polyubiquitin chains over Lys63-linked polyubiquitin chains, and it is capable of cleaving NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8), but not SUMO (small ubiquitin-related modifier) 1/2/3 and ISG15 (interferon-stimulated gene 15) conjugates. A functional comparison of OTUB1 and OTUB2 indicated a differential reactivity towards ubiquitin-based active-site probes carrying a vinyl methyl ester, a 2-chloroethyl or a 2-bromoethyl group at the C-terminus. Mutational analysis suggested that a narrow P1′ site, as observed in OTUB1, correlates with its ability to preferentially cleave Lys48-linked ubiquitin chains. Analysis of cellular interaction partners of OTUB1 by co-immunoprecipitation and MS/MS (tandem mass spectrometry) experiments demonstrated that FUS [fusion involved in t(12;6) in malignant liposarcoma; also known as TLS (translocation in liposarcoma) or CHOP (CCAAT/enhancer-binding protein homologous protein)] and RACK1 [receptor for activated kinase 1; also known as GNB2L1 (guanine-nucleotide-binding protein β polypeptide 2-like 1)] are part of OTUB1-containing complexes, pointing towards a molecular function of this deubiquitinating enzyme in RNA processing and cell adhesion/morphology. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1042/bj20081318 |
| الإتاحة: | https://doi.org/10.1042/bj20081318Test https://portlandpress.com/biochemj/article-pdf/418/2/379/658005/bj4180379.pdfTest |
| رقم الانضمام: | edsbas.B66A7E9B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1042/bj20081318 |
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