Universität zu Köln

de Boor, Susanne, Knyphausen, Philipp, Kuhlmann, Nora, Wroblowski, Sarah, Brenig, Julian, Scislowski, Lukas, Baldus, Linda, Nolte, Hendrik, Krueger, Marcus ORCID: 0000-0003-2008-4582 and Lammers, Michael ORCID: 0000-0003-4168-4640 (2015). Small GTP-binding protein Ran is regulated by posttranslational lysine acetylation. Proc. Natl. Acad. Sci. U. S. A., 112 (28). S. E3679 - 10. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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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 inmouse/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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code de Boor, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Knyphausen, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhlmann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Wroblowski, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Brenig, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED Scislowski, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Lammers, Michael UNSPECIFIED orcid.org/0000-0003-4168-4640 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-398850
DOI:	10.1073/pnas.1505995112
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	112
Number:	28
Page Range:	S. E3679 - 10
Date:	2015
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CRYSTAL-STRUCTURE; STRUCTURAL BASIS; NUCLEAR IMPORT; BIOCHEMICAL-CHARACTERIZATION; NUCLEOTIDE EXCHANGE; PROTEOMIC ANALYSIS; RCC1 PROTEIN; BETA; EXPORT; CHROMOSOME Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/39885