The rainbow trout CMP-sialic acid synthetase utilises a nuclear localization signal different from that identified in the mouse enzyme.

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Title The rainbow trout CMP-sialic acid synthetase utilises a nuclear localization signal different from that identified in the mouse enzyme.
Author Tiralongo, Giuseppe; Fujita, Akiko; Sato, Chihiro; Kitajima, Ken; Lehmann, Friederike; Oschiles, Melanie; Gerardy-Schahn, Rita; Munster-Kuhnel, Anja K
Journal Name Glycobiology
Year Published 2007
Place of publication London
Publisher Oxford University Press
Abstract The terminal sugar sialic acid (Sia) plays a pivotal role in cell–cell interaction and recognition. A prerequisite for the biosynthesis of sialoglycoconjugates is the activation of Sia to cytidine monophosphate-Sia (CMP-Sia), by CMP-Sia synthetases (CMP-Sia-syn). CMP-Sia-syn are conserved from bacteria to man, and have been found to reside in the nucleus of all vertebrate species analysed to date. We previously cloned the CMP-Sia-syn from rainbow trout (rt) and identified three clusters of basic amino acids (BC) that might act as nuclear localization signals (NLS). Here, we utilised chimeric proteins and rt CMP-Sia-syn mutants in which putative NLS sequences were deleted, to identify the nuclear transport signal. Divergent from the mouse enzyme, where the crucial NLS is part of the enzyme's active site, in the rt CMP-Sia-syn the NLS and active site are disparate. The crucial NLS in the fish enzyme is bipartite and the functionality depends on a free N-terminus. Comparative analysis of all putative rt NLS in mouse and fish cells identified a second inferior motif (rtBC5–6), which was functional only in fish cells suggesting some differences in transport mechanism or folding variabilities in fish. Moreover, based on computational analyses of putative CMP-Sia-syn from distant deuterostomian organisms it was concluded that CMP-Sia-syn nuclear localization is a relatively recent invention, originating in echinoderms. In summary, our data describing structural differences in the NLS of vertebrate CMP-Sia-syn, and the independence of Sia activation from the subcellular localization of the enzyme, provide supporting evidence that nuclear localization is linked to a second yet unknown function.
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Published Yes
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Copyright Statement Copyright 2007 authors. This is an open access paper. license that permits unrestricted use, provided that the paper is properly attributed.
Volume 17
Issue Number 9
Page from 945
Page to 954
ISSN 0959-6658
Date Accessioned 2008-02-25
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject PRE2009-Enzymes; PRE2009-Protein Targeting and Signal Transduction
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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