Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4.
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.
School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales, Australia. liza.cubeddu@sydney.edu.au
Liza
L
Cubeddu
Soumya
S
Joseph
Derek J
DJ
Richard
Jacqueline M
JM
Matthews
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D060588:LIM Domain Proteins / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C548809:Deaf1 protein, mouse; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D014157:Transcription Factors