Kuhlmann, Nora, Wroblowski, Sarah, Knyphausen, Philipp, de Boor, Susanne, Brenig, Julian, Zienert, Anke Y., Meyer-Teschendorf, Katrin, Praefcke, Gerrit J. K., Nolte, Hendrik, Krueger, Marcus, Schacherl, Magdalena ORCID: 0000-0002-5478-2509, Baumann, Ulrich, James, Leo C., Chin, Jason W. and Lammers, Michael ORCID: 0000-0003-4168-4640 (2016). Structural and Mechanistic Insights into the Regulation of the Fundamental Rho Regulator RhoGDI by Lysine Acetylation. J. Biol. Chem., 291 (11). S. 5484 - 5500. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

Rho proteins are small GTP/GDP-binding proteins primarily involved in cytoskeleton regulation. Their GTP/GDP cycle is often tightly connected to a membrane/cytosol cycle regulated by the Rho guanine nucleotide dissociation inhibitor (RhoGDI). RhoGDI has been regarded as a housekeeping regulator essential to control homeostasis of Rho proteins. Recent proteomic screens showed that RhoGDI is extensively lysine-acetylated. Here, we present the first comprehensive structural and mechanistic study to show how RhoGDI function is regulated by lysine acetylation. We discover that lysine acetylation impairs Rho protein binding and increases guanine nucleotide exchange factor-catalyzed nucleotide exchange on RhoA, these two functions being prerequisites to constitute a bona fide GDI displacement factor. RhoGDI acetylation interferes with Rho signaling, resulting in alteration of cellular filamentous actin. Finally, we discover that RhoGDI is endogenously acetylated in mammalian cells, and we identify CBP, p300, and pCAF as RhoGDI-acetyltransferases and Sirt2 and HDAC6 as specific deacetylases, showing the biological significance of this post-translational modification.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kuhlmann, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wroblowski, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knyphausen, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Boor, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenig, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zienert, Anke Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer-Teschendorf, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Praefcke, Gerrit J. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schacherl, MagdalenaUNSPECIFIEDorcid.org/0000-0002-5478-2509UNSPECIFIED
Baumann, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
James, Leo C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chin, Jason W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lammers, MichaelUNSPECIFIEDorcid.org/0000-0003-4168-4640UNSPECIFIED
URN: urn:nbn:de:hbz:38-281587
DOI: 10.1074/jbc.M115.707091
Journal or Publication Title: J. Biol. Chem.
Volume: 291
Number: 11
Page Range: S. 5484 - 5500
Date: 2016
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication: BETHESDA
ISSN: 1083-351X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GDP DISSOCIATION INHIBITOR; STRUCTURE VALIDATION; CELL-MIGRATION; BINDING; GTPASE; PHOSPHORYLATION; PROTEIN; COMPLEX; SIRT2; HDAC6Multiple languages
Biochemistry & Molecular BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28158

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