Browse by author
Lookup NU author(s): Laura Evans, Dr Lindi Chen, Dr Elaine WillmoreORCiD, Professor Herbie Newell, Professor Deborah Tweddle
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
SKP2 is the substrate recognition subunit of the ubiquitin ligase complex which targets p27(KIP1) for degradation. Induced at the G(1)/S transit of the cell cycle, SKP2 is frequently overexpressed in human cancers and contributes to malignancy. We previously identified SKP2 as a possible MYCN target gene and hence hypothesise that SKP2 is a potential therapeutic target in MYCN amplified disease. A positive correlation was identified between MYCN activity and SKP2 mRNA expression in Tet21N MYCN-regulatable cells and a panel of MYCN amplified and non-amplified neuroblastoma cell lines. In chromatin immunoprecipitation and reporter gene assays, MYCN bound directly to E-boxes within the SKP2 promoter and induced transcriptional activity which was decreased by the removal of MYCN and E-box mutation. Although SKP2 knockdown inhibited cell growth in both MYCN amplified and non-amplified cells, cell cycle arrest and apoptosis were induced only in non-MYCN amplified neuroblastoma cells. In conclusion these data identify SKP2 as a direct transcriptional target of MYCN and supports SKP2 as a potential therapeutic target in neuroblastoma. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Author(s): Evans L, Chen L, Milazzo G, Gherardi S, Perini G, Willmore E, Newell DR, Tweddle DA
Publication type: Article
Publication status: Published
Journal: Cancer Letters
Year: 2015
Volume: 363
Issue: 1
Pages: 37-45
Print publication date: 10/07/2015
Online publication date: 02/04/2015
Acceptance date: 28/03/2015
ISSN (print): 0304-3835
ISSN (electronic): 1872-7980
Publisher: Elsevier
URL: http://dx.doi.org/10.1016/j.canlet.2015.03.044
DOI: 10.1016/j.canlet.2015.03.044
Altmetrics provided by Altmetric