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Ubiquitin Chains: Degradation and Beyond (Hardcover, 2015 ed.)
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Ubiquitin Chains: Degradation and Beyond (Hardcover, 2015 ed.)
Series: Springer Theses
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This 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.
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