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Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):E3679-88. doi: 10.1073/pnas.1505995112. Epub 2015 Jun 29.

Small GTP-binding protein Ran is regulated by posttranslational lysine acetylation.

Author information

1
Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
2
Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany michael.lammers@uni-koeln.de.

Abstract

Ran is a small GTP-binding protein of the Ras superfamily regulating fundamental cellular processes: nucleo-cytoplasmic transport, nuclear envelope formation and mitotic spindle assembly. An intracellular Ran•GTP/Ran•GDP gradient created by the distinct subcellular localization of its regulators RCC1 and RanGAP mediates many of its cellular effects. Recent proteomic screens identified five Ran lysine acetylation sites in human and eleven sites in mouse/rat tissues. Some of these sites are located in functionally highly important regions such as switch I and switch II. Here, we show that lysine acetylation interferes with essential aspects of Ran function: nucleotide exchange and hydrolysis, subcellular Ran localization, GTP hydrolysis, and the interaction with import and export receptors. Deacetylation activity of certain sirtuins was detected for two Ran acetylation sites in vitro. Moreover, Ran was acetylated by CBP/p300 and Tip60 in vitro and on transferase overexpression in vivo. Overall, this study addresses many important challenges of the acetylome field, which will be discussed.

KEYWORDS:

Ran; genetic code expansion concept; lysine acetylation; nuclear cytosolic transport; nucleus

PMID:
26124124
PMCID:
PMC4507232
DOI:
10.1073/pnas.1505995112
[Indexed for MEDLINE]
Free PMC Article

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