LEADER 05028nam 22006615 450 001 9910298291003321 005 20200630183749.0 010 $a3-319-14965-2 024 7 $a10.1007/978-3-319-14965-3 035 $a(CKB)3710000000375628 035 $a(EBL)1998175 035 $a(SSID)ssj0001465048 035 $a(PQKBManifestationID)11820883 035 $a(PQKBTitleCode)TC0001465048 035 $a(PQKBWorkID)11458992 035 $a(PQKB)10312309 035 $a(DE-He213)978-3-319-14965-3 035 $a(MiAaPQ)EBC1998175 035 $a(PPN)184896436 035 $a(EXLCZ)993710000000375628 100 $a20150310d2015 u| 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 10$aUbiquitin Chains: Degradation and Beyond /$fby Arnab De 205 $a1st ed. 2015. 210 1$aCham :$cSpringer International Publishing :$cImprint: Springer,$d2015. 215 $a1 online resource (119 p.) 225 1 $aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 300 $aDescription based upon print version of record. 311 $a3-319-14964-4 320 $aIncludes bibliographical references at the end of each chapters and index. 327 $a1 Immune homeostasis: Activation and Downregulation of NF-?B -- 2 Regulation of NF-?B signaling by regulatory ubiquitination: specific pathways and A20 -- 3 The deubiquitinase activity of A20 is dispensable for its role in NF-?B signaling -- 4 Perspectives on regulatory ubiquitination. 330 $aThis thesis examines the evidence for regulatory ubiquitination by focusing on A20. It provides an insightful and in-depth evaluation of the current literature by critically examining the evidence of K63-linked regulatory ubiquitination in regulating cell-signalling. It is also the first thesis to directly test the role of regulatory ubiquitination in NF-kB signaling in vivo. The case for regulatory ubiquitination has been to a large extent predicated upon the presumed deubiquitinase activity of A20, long considered a key regulator of inflammatory responses as mice lacking A20 die from multi-organ inflammation and cachexia. The theses reports the creation and characterization of a knock-in mouse that expresses a mutated form of A20 which selectively lacks the deubiquitinase activity. The knock-in mice surprisingly display completely normal NF-?B activation with no accompanying inflammatory phenotype. Given that the presumed role of A20 as a deubiquitinase has been used to support the importance of regulatory K63-linked ubiquitination in NF-kB signaling, this study will help focus future research efforts into alternative target pathways that do not depend on K63 ubiquitination. In fact, the work suggests that it might be important to revisit the role of K63-linked polyubiquitination in cell-signalling. Ubiquitin Chains: Degradation and Beyond is essential reading for anyone conducting research in cell-signalling and immunology. Dr. Arnab De received his PhD from the Department of Microbiology & Immunology at Columbia University. During his PhD, he developed transgenic mice to study the mechanism of action of a critical tumor-suppressor called A20. He is also well known for having developed peptide-based prodrugs as therapeutics for diabetes. His work has been reported by the media, and has resulted in multiple patents and publications in peer reviewed journals. He presented his findings at the American Peptide Symposium and was awarded the Young Investigator?s Award. He is the author of the book entitled Application of Peptide-Based Prodrug Chemistry in Drug Development, with a foreword written by Professor Jean Martinez (Former President, European Peptide Society) and published in the series SpringerBriefs in Pharmaceutical Science & Drug Development. His research interests lie at the intersection of chemistry and medicine.  Besides biomedical research, he is also generally interested in public health policy and general scientific outreach. 410 0$aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 606 $aProteins  606 $aCell cycle 606 $aImmunology 606 $aProtein Science$3https://scigraph.springernature.com/ontologies/product-market-codes/L14040 606 $aCell Cycle Analysis$3https://scigraph.springernature.com/ontologies/product-market-codes/L16030 606 $aImmunology$3https://scigraph.springernature.com/ontologies/product-market-codes/B14000 615 0$aProteins . 615 0$aCell cycle. 615 0$aImmunology. 615 14$aProtein Science. 615 24$aCell Cycle Analysis. 615 24$aImmunology. 676 $a574.19245 700 $aDe$b Arnab$4aut$4http://id.loc.gov/vocabulary/relators/aut$0964068 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910298291003321 996 $aUbiquitin Chains: Degradation and Beyond$92536142 997 $aUNINA