BRD4 Short Isoform Interacts with RRP1B, SIPA1 and Components of the LINC Complex at the Inner Face of the Nuclear Membrane
Year: 2013
Type: article
Abstract: Recent studies suggest that BET inhibitors are effective anti-cancer therapeutics. Here we show that BET inhibitors are effective against murine primary mammary tumors, but not pulmonary metastases. BRD4, a target of BET inhibitors, encodes two isoforms with opposite effects on tumor progression. To gain insights into why BET inhibition was ineffective against metastases the pro-metastatic short isoform of BRD4 was characterized using mass spectrometry and cellular fractionation. Our data show that the pro-metastatic short isoform interacts with the LINC complex and the metastasis-associated proteins RRP1B and SIPA1 at the inner face of the nuclear membrane. Furthermore, histone binding arrays revealed that the short isoform has a broader acetylated histone binding pattern relative to the long isoform. These differential biochemical and nuclear localization properties revealed in our study provide novel insights into the opposing roles of BRD4 isoforms in metastatic breast cancer progression.
Source: PLoS ONE
Authors: Jude Alsarraj, Farhoud Faraji, Thomas R. Geiger, Katherine R. Mattaini, Mia Williams, Josephine Wu, Ngoc-Han Ha, Tyler Merlino, Renard C. Walker, Allen D. Bosley, Zhen Xiao, Thorkell Andresson, Dominic Esposito, Nicholas Smithers, Dave Lugo, Rab Prinjha, Anup Day, Nigel P. S. Crawford, Keiko Ozato, Kevin Gardner, Kent W. Hunter
Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research, Saint Louis University, Frederick National Laboratory for Cancer Research, GlaxoSmithKline (United Kingdom), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Human Genome Research Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1110894908, G9000151220
OpenAlex ID: W2057519700