In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Related resources

Full-text held externally

University researcher(s)

BCR/ABL modulates protein phosphorylation associated with the etoposide-induced DNA damage response.

Griaud, François; Williamson, Andrew J K; Taylor, Samuel; Potier, David N; Spooncer, Elaine; Pierce, Andrew; Whetton, Anthony D

Journal of proteomics. 2012;77:14-26.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:

Full-text held externally

Abstract

BCR/ABL expression is the key characteristic of chronic myeloid leukaemia (CML). The progression of CML is associated with genomic instability. Systematic analysis of DNA damage signalling in the presence of BCR/ABL thus offers opportunities to identify mechanisms of leukaemic progression. We therefore undertook a quantitative phosphoproteomics study to test whether BCR/ABL expression could globally affect the response to genotoxic stress signalling. Etoposide-induced DNA damage was chosen and the concentration and time of exposure determined such that apoptosis was not associated with the study. More than 1100 phosphoentities were identified. BCR/ABL was shown to significantly alter the response to etoposide in many cases. These include sites on MDC1, a key component of DNA repair, and Hemogen. Hemogen is a transcriptional target of HOXB4 and GATA1, two transcription factors involved in haemopoietic development, and is overexpressed in acute myeloid leukaemia. To validate Hemogen phosphorylation, absolute quantification using an isotopomeric standard and selected reaction monitoring was performed. This revealed a strong correlation with isobaric tagging data and offering quantification at about 10 fmol per million cells. Furthermore we found that multiple protein phosphorylation changes mediated by BCR/ABL were connected to the increased activation of NFκB, a key survival transcription factor, after etoposide exposure.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Published date:
Journal title:
Abbreviated journal title:
ISSN:
Place of publication:
Netherlands
Volume:
77
Pagination:
14-26
Digital Object Identifier:
10.1016/j.jprot.2012.06.003
Pubmed Identifier:
22705319
Pii Identifier:
S1874-3919(12)00427-7
Access state:
Active

Institutional metadata

University researcher(s):
Academic department(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:219337
Created by:
Whetton, Anthony
Created:
14th February, 2014, 14:01:04
Last modified by:
Whetton, Anthony
Last modified:
1st February, 2015, 19:12:54

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.