BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c2c9aa744b3a4146a566e38515814caa
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spelling	oai:doaj.org-article:c2c9aa744b3a4146a566e38515814caa2021-11-18T08:45:44ZBRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.1932-620310.1371/journal.pone.0080746https://doaj.org/article/c2c9aa744b3a4146a566e38515814caa2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24260471/?tool=EBIhttps://doaj.org/toc/1932-6203Recent 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.Jude AlsarrajFarhoud FarajiThomas R GeigerKatherine R MattainiMia WilliamsJosephine WuNgoc-Han HaTyler MerlinoRenard C WalkerAllen D BosleyZhen XiaoThorkell AndressonDominic EspositoNicholas SmithersDave LugoRab PrinjhaAnup DayNigel P S CrawfordKeiko OzatoKevin GardnerKent W HunterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80746 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.
description	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.
format	article
author	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
author_facet	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
author_sort	Jude Alsarraj
title	BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.
title_short	BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.
title_full	BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.
title_fullStr	BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.
title_full_unstemmed	BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.
title_sort	brd4 short isoform interacts with rrp1b, sipa1 and components of the linc complex at the inner face of the nuclear membrane.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c2c9aa744b3a4146a566e38515814caa
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BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.

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