English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Galectin-8 binds to the farnesylated C-terminus of K-Ras4B and modifies Ras/ERK signaling and migration in pancreatic and lung carcinoma cells

Meinohl, C., Barnard, S. J., Fritz-Wolf, K., Unger, M., Porr, A., Heipel, M., et al. (2019). Galectin-8 binds to the farnesylated C-terminus of K-Ras4B and modifies Ras/ERK signaling and migration in pancreatic and lung carcinoma cells. Cancers, 12(1), 30-54. doi:10.3390/cancers12010030.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0005-6DAB-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-6DAC-0
Genre: Journal Article

Files

show Files
hide Files
:
Cancers_12_2020_30.pdf (Any fulltext), 3MB
 
File Permalink:
-
Name:
Cancers_12_2020_30.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Medical Research, MHMF; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-
Locator:
https://doi.org/10.3390/cancers12010030 (Any fulltext)
Description:
-

Creators

show
hide
 Creators:
Meinohl, Christopher, Author
Barnard, Sarah J., Author
Fritz-Wolf, Karin1, 2, Author              
Unger, Monika, Author
Porr, Andreea, Author
Heipel, Marisa, Author
StefanieWirth, Author
Madlung, Johannes, Author
Nordheim, Alfred, Author
Menke, Andre, Author
Becker, Katja, Author
Giehl, Klaudia, Author
Affiliations:
1Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society, ou_1497700              
2Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497712              

Content

show
hide
Free keywords: K-Ras4B; Galectin-8; signal transduction; ERK; lung and pancreatic carcinoma; migration; proliferation
 Abstract: K-Ras is the most prominent driver of oncogenesis and no effective K-Ras inhibitors have been established despite decades of intensive research. Identifying new K-Ras-binding proteins and their interaction domains offers the opportunity for defining new approaches in tackling oncogenic K-Ras. We have identified Galectin-8 as a novel, direct binding protein for K-Ras4B by mass spectrometry analyses and protein interaction studies. Galectin-8 is a tandem-repeat Galectin and it is widely expressed in lung and pancreatic carcinoma cells. siRNA-mediated depletion of Galectin-8 resulted in increased K-Ras4B content and ERK1/2 activity in lung and pancreatic carcinoma cells. Moreover, cell migration and cell proliferation were inhibited by the depletion of Galectin-8. The K-Ras4B–Galectin-8 interaction is indispensably associated with the farnesylation of K-Ras4B. The lysine-rich polybasic domain (PBD), a region that is unique for K-Ras4B as compared to H- and N-Ras, stabilizes the interaction and accounts for the specificity. Binding assays with the deletion mutants of Galectin-8, comprising either of the two carbohydrate recognition domains (CRD), revealed that K-Ras4B only interacts with the N-CRD, but not with the C-CRD. Structural modeling uncovers a potential binding pocket for the hydrophobic farnesyl chain of K-Ras4B and a cluster of negatively charged amino acids for interaction with the positively charged lysine residues in the N-CRD. Our results demonstrate that Galectin-8 is a new binding partner for K-Ras4B and it interacts via the N-CRD with the farnesylated PBD of K-Ras, thereby modulating the K-Ras effector pathways as well as cell proliferation and migration.

Details

show
hide
Language(s): eng - English
 Dates: 2019-12-032019-12-172019-12-202019-12-20
 Publication Status: Published in print
 Pages: 24
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Cancers
  Alternative Title : Molecular Diversity Preservation International (MDPI)
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Basel : MDPI
Pages: - Volume / Issue: 12 (1) Sequence Number: - Start / End Page: 30 - 54 Identifier: ISSN: 2072-6694