contribution of deaf1 structural domains to the interaction with the breast cancer oncogene lmo4的贡献deaf1结构域与乳腺癌致癌基因lmo4的交互.pdf

Contribution of DEAF1 Structural Domains to the Interaction with the Breast Cancer Oncogene LMO4 1 ¤ 1 2 1 Liza Cubeddu * , Soumya Joseph , Derek J. Richard , Jacqueline M. Matthews * 1 School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales, Australia, 2 Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia Abstract The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1. Citation: Cubeddu L, Joseph S, Richard DJ, Matthews JM (2012) Contribution of DEAF1 Structural Domains to the Interaction with the Breast Cancer Oncogene LMO4. PLoS ONE 7(6): e39218. doi:10.1371/journal.pone.0039218 Editor: Bin Xue, University of South Florida, United States of America Received January 11, 2012; Accepted May 17, 2012; Published June 19, 2012 Copyright: 2012 Cubeddu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted u