Universität zu Köln

Knyphausen, Philipp, Lang, Franziska, Baldus, Linda, Extra, Antje and Lammers, Michael (2016). Insights into K-Ras 4B regulation by post-translational lysine acetylation. Biol. Chem., 397 (10). S. 1071 - 1086. BERLIN: WALTER DE GRUYTER GMBH. ISSN 1437-4315

Full text not available from this repository.

Abstract

Ras is a molecular switch cycling between an active, GTP-bound and an inactive, GDP-bound state. Mutations in Ras, mostly affecting the off-switch, are found in many human tumours. Recently, it has been shown that K-Ras 4B is targeted by lysine acetylation at K104. Based on results obtained for an acetylation mimetic Ras mutant (K104Q), it was hypothesised that K104-acetylation might interfere with its oncogenicity by impairing SOS-catalysed guanine-nucleotide exchange. We prepared site-specifically K104-acetylated K-Ras 4B and the corresponding oncogenic mutant protein G12V using the genetic-code expansion concept. We found that SOS-catalysed nucleotide exchange, also of allosterically activated SOS, was neither affected by acetylation of K104 in wildtype K-Ras 4B nor in the G12V mutant, suggesting that glutamine is a poor mimetic for acetylation at this site. In vitro, the lysine-acetyltransferases CBP and p300 were able to acetylate both, wildtype and G12V K-Ras 4B. In addition to K104 we identified further acetylation sites in K-Ras 4B, including K147, within the important G5/SAK-motif. However, the intrinsic and the SOS-catalysed nucleotide exchange was not affected by K147-acetylation of K-Ras 4B. Finally, we show that Sirt2 and HDAC6 do neither deacetylate K-Ras 4B if acetylated at K104 nor if acetylated at K147 in vitro.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knyphausen, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Extra, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Lammers, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-260853
DOI:	10.1515/hsz-2016-0118
Journal or Publication Title:	Biol. Chem.
Volume:	397
Number:	10
Page Range:	S. 1071 - 1086
Date:	2016
Publisher:	WALTER DE GRUYTER GMBH
Place of Publication:	BERLIN
ISSN:	1437-4315
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ONCOGENIC RAS; COSTELLO-SYNDROME; NOONAN-SYNDROME; SIGNALING PATHWAY; G-PROTEINS; B-RAF; N-RAS; CARDIOFACIOCUTANEOUS SYNDROME; TRIPHOSPHATE CONFORMATION; TUMOR PROGRESSION Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26085