English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Balance of human choline kinase isoforms is critical for cell cycle regulation: Implications for the development of choline kinase-targeted cancer therapy.

Gruber, J., See Too, W. C., Wong, M. T., Lavie, A., McSorley, T., & Konrad, M. (2012). Balance of human choline kinase isoforms is critical for cell cycle regulation: Implications for the development of choline kinase-targeted cancer therapy. FEBS Journal, 279(11), 1915-1928. doi:10.1111/j.1742-4658.2012.08573.x.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-9DA6-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-E5A7-6
Genre: Journal Article

Files

show Files
hide Files
:
1478278.pdf (Publisher version), 786KB
Name:
1478278.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1478278_sm_FigS1-S3.zip (Supplementary material), 327KB
Name:
1478278_sm_FigS1-S3.zip
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/zip / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Gruber, J.1, Author              
See Too, W. C.1, Author              
Wong, M. T., Author
Lavie, A., Author
McSorley, T.1, Author              
Konrad, M.1, Author              
Affiliations:
1Research Group of Enzyme Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578612              

Content

show
hide
Free keywords: Anti-cancer strategy; cell cycle regulation; choline kinase; siRNA knockdown; subcellular localization
 Abstract: The enzyme choline kinase (CK), which catalyzes the phosphorylation of choline to phosphorylcholine in the presence of ATP, has an essential role in the biosynthesis of phosphatidylcholine, the major constituent of all mammalian cell membranes. CK is encoded by two separate genes expressing the three isoforms CKα1, CKα2 and CKβ that are active as homodimeric or heterodimeric species. Metabolic changes observed in various cancer cell lines and tumors have been associated with differential and marked up-regulation of the CKα genes, and specific inhibition of CKα activity has been proposed as a potential anti-cancer strategy. As a result, less attention has been given to CKβ and its interaction with CKα. With the aim of profiling the intracellular roles of CKα and CKβ, we used RNA interference (RNAi) as a molecular approach to down-regulate the expression of CK in HeLa cells. Individual and simultaneous RNAi-based silencing of the CK α and β isoforms was achieved using different combinations of knockdown strategies. Efficient knockdown was confirmed by immunodetection using our isoform-specific antibodies and by quantitative real-time PCR. Our analyses of the phenotypic consequences of CK depletion showed the expected lethal effect of CKα knockdown. However, CKβ- and CKα + CKβ-silenced cells had no aberrant phenotype. Therefore, our results support the hypothesis that the balance of the α and β isoforms is critical for cancer cell survival. The suppression of the cancer cell killing effect of CKα silencing by simultaneous knockdown of both isoforms implies that a more effective CK-based anti-cancer strategy can be achieved by reducing cross-reactivity with CKβ.

Details

show
hide
Language(s): eng - English
 Dates: 2012-04-162012-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1111/j.1742-4658.2012.08573.x
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: FEBS Journal
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 279 (11) Sequence Number: - Start / End Page: 1915 - 1928 Identifier: -