Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform
Autor: | Mathias Ziegler, Timo Lutter, Johannes Gregor Matthias Rack, Rein Aasland, Magali R. VanLinden |
---|---|
Rok vydání: | 2013 |
Předmět: |
Gene isoform
Models Molecular Protein Folding Protein Conformation Static Electricity SIRT2 Sirtuin 2 Structural Biology Catalytic Domain RNA Precursors Humans Protein Isoforms Nuclear protein Nuclear export signal Molecular Biology Cell Nucleus Nuclear Export Signals biology Alternative splicing Recombinant Proteins Protein Structure Tertiary Alternative Splicing HEK293 Cells Biochemistry Sirtuin biology.protein 5' Untranslated Regions Nuclear localization sequence Deacetylase activity HeLa Cells |
Zdroj: | Journal of molecular biology. 426(8) |
ISSN: | 1089-8638 |
Popis: | Sirtuin-2 (SIRT2), the cytoplasmic member of the sirtuin family, has been implicated in the deacetylation of nuclear proteins. Although the enzyme has been reported to be located to the nucleus during G2/M phase, its spectrum of targets suggests functions in the nucleus throughout the cell cycle. While a nucleocytoplasmic shuttling mechanism has been proposed for SIRT2, recent studies have indicated the presence of a constitutively nuclear isoform. Here we report the identification of a novel splice variant (isoform 5) of SIRT2 that lacks a nuclear export signal and encodes a predominantly nuclear isoform. This novel isoform 5 fails to show deacetylase activity using several assays, both in vitro and in vivo, and we are led to conclude that this isoform is catalytically inactive. Nevertheless, it retains the ability to interact with p300, a known interaction partner. Moreover, changes in intrinsic tryptophan fluorescence upon denaturation indicate that the protein is properly folded. These data, together with computational analyses, confirm the structural integrity of the catalytic domain. Our results suggest an activity-independent nuclear function of the novel isoform. |
Databáze: | OpenAIRE |
Externí odkaz: |