Klimpel, Annika, Stillger, Katharina, Wiederstein, Janica L., Krueger, Marcus and Neundorf, Ines . Cell-permeable CaaX-peptides affect K-Ras downstream signaling and promote cell death in cancer cells. FEBS J.. HOBOKEN: WILEY. ISSN 1742-4658

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Abstract

Cysteine prenylation is a post-translational modification that is used by nature to control crucial biological functions of proteins, such as membrane trafficking, signal transduction, and apoptosis. It mainly occurs in eukaryotic proteins at a C-terminal CaaX box and is mediated by prenyltransferases. Since the discovery of prenylated proteins, various tools have been developed to study the mechanisms of prenyltransferases, as well as to visualize and to identify prenylated proteins. Herein, we introduce cell-permeable peptides bearing a C-terminal CaaX motif based on Ras sequences. We demonstrate that intracellular accumulation of those peptides in different cells is controlled by the presence of their CaaX motif and that they specifically interact with intracellular prenyltransferases. As proof of concept, we further highlight their utilization to alter downstream signaling of Ras proteins, particularly of K-Ras-4B, in pancreatic cancer cells. Application of this strategy holds great promise to better understand and regulate post-translational cysteine prenylation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Klimpel, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stillger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiederstein, Janica L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neundorf, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-311970
DOI: 10.1111/febs.15612
Journal or Publication Title: FEBS J.
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1742-4658
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PENETRATING PEPTIDE; FARNESYLTRANSFERASE INHIBITORS; PRENYLATED PEPTIDES; N-RAS; PROTEIN; KRAS; GERANYLGERANYLTRANSFERASE; LOCALIZATION; ORGANIZATION; ISOPRENOIDSMultiple languages
Biochemistry & Molecular BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31197

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