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Supplements to article: A novel transcription complex that selectively modulates apoptosis of breast cancer cells through regulation of FASTKD2

Authors: Yeung, Kay T.
Das, Sharmistha
Lomniczi, Alejandro
Ojeda, Sergio R.
Xu, Chong-Feng
Neubert, Thomas A.
Samuels, Herbert H.
Keywords: apoptosis;breast cancer;mass spectrometry;IRF-2BP2;FASTKD2
Issue Date: 23-Mar-2011
Abstract: (This refers to the article.) We previously reported that expression of NRIF3 (Nuclear Receptor Interacting Factor-3) rapidly and selectively leads to apoptosis of breast cancer cells. DIF-1 (a.k.a IRF-2BP2), the cellular target of NRIF3, was identified as a transcriptional repressor and DIF-1 knockdown leads to apoptosis of breast cancer cells but not other cell types. Here, we identify IRF2BP1 (Interferon Regulatory Factor-2 Binding Protein 1) and EAP1 (Enhanced At Puberty 1) as important components of the DIF-1 complex mediating both complex stability and transcriptional repression. This interaction of DIF-1, IRF2BP1, and EAP1 occurs through the conserved C4 zinc-fingers of these proteins. Microarray studies were carried out in breast cancer cell lines engineered to conditionally and rapidly increase the levels of the Death Domain region of NRIF3 (DD1). The DIF-1 complex was found to repress FASTKD2, a putative pro-apoptotic gene, in breast cancer cells and to bind to the FASTKD2 gene by chromatin immunoprecipitation. FASTKD2 knockdown prevents apoptosis of breast cancer cells from NRIF3 expression or DIF-1 knockdown while expression of FASTKD2 leads to apoptosis of both breast and non-breast cancer cells. Thus, regulation of FASTKD2 by NRIF3 and the DIF-1 complex acts as a novel death switch that selectively modulates apoptosis in breast cancer.
Description: The materials provided here are supplemental tables and figures to an article to be published in 'Molecular and Cellular Biology.'
Appears in Collections:Herbert Samuels Collection

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Yeung-MCB-2011-Supplemental Figure and Table Legends.pdfFigure and table legends107.7 kBAdobe PDFView/Open
Yeung-MCB-2011-Supplemental-Figs-1-7.pdfSupplemental figures 1-72.63 MBAdobe PDFView/Open
Yeung-MCB-2011-Supplemental-Tables-1-3.pdfSupplmental tables 1-3121.19 kBAdobe PDFView/Open

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