Universität zu Köln

Klußmann, Merlin ORCID: 0000-0001-6041-0501, Matijass, Martin and Neundorf, Ines ORCID: 0000-0001-6450-3991 (2025). Impact of Mutational Status on Intracellular Effects of Cell‐Permeable CaaX Peptides in Pancreatic Cancer Cells. ChemBioChem, 26 (10). pp. 1-11. Wiley. ISSN 1439-4227

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Abstract

[Artikel-Nr.: e20240107] Prenyltransferases add a lipid group to the cysteine of a CaaX motif of proteins. This posttranslational modification enables proteins to attach to membranes where they are essential hubs for signaling, trafficking, and apoptosis. Recently, cell‐permeable CaaX‐peptides are developed as possible tools to interfere with the prenylation machinery. These peptides cause cytotoxic effects, particularly in KRas mutant pancreatic cancer cells (PANC‐1) in which they also alter downstream signaling of Ras proteins. Herein, the aim is to get more clues about the relevance of the mutational status of KRas. Therefore, the activity of CaaX‐peptides in KRas wildtype BxPC‐3 and KRas mutated PANC‐1 cells is compared. CaaX‐peptides differently influence these two cell lines, although they internalize pretty much to the same extent. Indeed, an altered KRas plasma membrane localization in PANC‐1 cells is observed, probably induced by disturbed KRas prenylation based on the presence of CaaX‐peptides. The impact of CaaX‐peptides on KRas signaling is likely dependent on the KRas mutation in PANC‐1 cells in which they further trigger effects on KRas‐dependent regulators, e.g., Neurofibromin −1 (NF1) and son of sevenless homolog 1 (SOS1). All in all, CaaX peptides are identified as promising tools for studying and manipulating the function of therapeutically important prenylated proteins.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Klußmann, Merlin UNSPECIFIED https://orcid.org/0000-0001-6041-0501 UNSPECIFIED Matijass, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, Ines UNSPECIFIED https://orcid.org/0000-0001-6450-3991 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-802624
Identification Number:	10.1002/cbic.202401076
Journal or Publication Title:	ChemBioChem
Volume:	26
Number:	10
Page Range:	pp. 1-11
Number of Pages:	11
Date:	27 May 2025
Publisher:	Wiley
ISSN:	1439-4227
Language:	English
Faculty:	External institution Faculty of Mathematics and Natural Sciences
Divisions:	Außeruniversitäre Forschungseinrichtungen > Forschungszentrum Jülich Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	Chemistry and allied sciences Life sciences
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80262