Browse by author
Lookup NU author(s): Lorenzo Aulisa, Dr Nicolas Forraz, Professor Colin McGuckin
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
HOX genes encode conserved transcription factors that control the morphological diversification along the anteroposterior body axis. HOX proteins bind to DNA through a highly conserved 60 amino acid sequence called the homeodomain, and greater DNA binding specificity and stability are achieved when it forms complexes with cofactors such as PBX and MEIS in humans. In particular, HOX proteins from paralog groups 1-8, interact with PBX proteins via a specific and highly conserved hydrophobic six amino acid sequence localized in the N-terminal region of HOX. In several oncogenic transformations, deregulated HOX gene expression has been observed, indicating an involvement of these transcriptional regulators in carcinogenesis and metastasis. Inhibition of the HOX-PBX interaction could be a strategy to control the abnormal proliferation of these cancer cells. In this study we describe a small designed peptide amphiphile (PA) which self-assembles into micelles and shows inhibition of T3M4 pancreatic cancer cells, K562 leukemia cells and MJT1 melanoma cells while non-cancerous fibroblast NIH 3T3 cells are less affected. This molecule contains three critical regions: a 9-amino-acid sequence designed to disrupt HOX/PBX/DNA complex formation, a 16-amino-acid sequence to deliver the peptide into the cell and a t6-carbon-acyl chain which we show leads to the molecule's self-assembly and significantly enhances the effectiveness of the molecule to slow cell proliferation. (c) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Author(s): Aulisa L, Forraz N, McGuckin C, Hartgerink JD
Publication type: Article
Publication status: Unknown
Journal: Acta Biomaterialia
Year: 2009
Volume: 5
Issue: 3
Pages: 842-853
ISSN (print): 1742-7061
ISSN (electronic): 1878-7568
Publisher: Elsevier BV
URL: .http:/dx.doi.org/10.1016/j.actbio.2008.11.002
DOI: 10.1016/j.actbio.2008.11.002
Altmetrics provided by Altmetric
