BRD4 Short Isoform Interacts with RRP1B, SIPA1 and Components of the LINC Complex at the Inner Face of the Nuclear Membrane

Alsarraj, Jude; Faraji, Farhoud; Geiger, Thomas; Mattaini, Katherine; Williams, Mia; Wu, Josephine J.; Ha, Ngoc-Han; Merlino, T.; Walker, Renard C.; Bosley, Allen D.; Xiao, Zhen; Andrésson, Þorkell; Esposito, Dominic; Smithers, Nicholas; Lugo, Dave; Prinjha, Rab K.; Day, Anup; Crawford, Nigel P.S.; Ozato, Keiko; Gardner, Kevin; Hunter, Kent W.

doi:10.1371/journal.pone.0080746

Cited by 56 publications

(64 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have suggested that SIPA-1 is involved in certain types of cancer activity, including mutation (23,24), apoptosis (12,25), proliferation (4,15), invasion (15,16) and metastasis (13,26,27). In the present study, it was observed that SIPA-1 additionally regulates bladder cancer cell metastasis and invasion (Figs.…”

Section: Discussionsupporting

confidence: 61%

Suppression of SIPA-1 expression may reduce bladder cancer invasion and metastasis via the downregulation of E-cadherin and ZO-1

Zhang

Wang

2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. The aim of the present study was to investigate the capacity of signal-induced proliferation-associated protein 1 (SIPA-1) to regulate bladder cancer cell invasion and metastasis. BIU-87 and T24 cells were transfected with the SIPA gene and SIPA short hairpin (sh)RNA, respectively. Western blot analysis was conducted to analyze the expression levels of SIPA-1, Ras-related protein 1 (Rap1), Rap1 guanosine triphosphate (Rap1GTP), E-cadherin and zona occludens-1 (ZO-1). Cell motility and invasion were evaluated in vitro using wound and Transwell assays. Transfected cells were inoculated into the pelvic region of BALB/c nude mice, and the number of resulting tumors was recorded after 6 weeks. Western blot analysis revealed that expression levels of E-cadherin and ZO-1 were reduced in the cells with enhanced levels of SIPA-1. By contrast, the levels of E-cadherin and ZO-1 were elevated in the cells in which SIPA-1 was knocked down. In comparison with untransfected cells, the cells with reduced levels of SIPA-1 exhibited reduced wound closure and fewer cells crossed the chamber in the Transwell experiment, whereas the cells with enhanced levels of SIPA-1 exhibited increased migration and invasion In vivo, an increased tumor count was obtained in the mice with elevated levels of SIPA-1. Therefore, the results of the present study indicate that SIPA-1 is able to regulate bladder cancer cell metastasis and invasion by reducing the expression of E-cadherin and ZO-1.

show abstract

Section: Discussionsupporting

confidence: 61%

Suppression of SIPA-1 expression may reduce bladder cancer invasion and metastasis via the downregulation of E-cadherin and ZO-1

Zhang

Wang

2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…For example, BRD4 exists in 2 different isoforms generated by alternative splicing that—in oncology—exert opposite effects. Mass spectrometry revealed that the short isoform is pro-metastatic and also has a broader acetylated histone binding pattern relative to the long isoform 28 . The role of the different isoforms in inflammation has however not yet been explored.…”

Section: Inflammationmentioning

confidence: 99%

Chemical probes targeting epigenetic proteins: Applications beyond oncology

Ackloo

Brown

Müller³

2017

Epigenetics

View full text Add to dashboard Cite

Epigenetic chemical probes are potent, cell-active, small molecule inhibitors or antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about 4 thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro. Epigenetic chemical probes have been critical tools in oncology research and have uncovered mechanistic insights into well-established targets, as well as identify new therapeutic starting points. Indeed, the literature primarily links epigenetic proteins to oncology, but applications in inflammation, viral, metabolic and neurodegenerative diseases are now being reported. We summarize the literature of these emerging applications and provide examples where existing probes might be used.

show abstract

“…Accordingly, the level of expression of NET23/STING roughly correlates with the extent of chromatin compaction in the various cell types examined [69]. SUN2 binds the chromatin remodeler BRD4 [70]. LAP2β binds histone deacetylase 3 (HDAC3) [71] and, in co-complex with lamin B1, influences the positioning of several lymphocyte-specific genes [72].…”

Section: The Two Faces Of the Ne — Tissue-specific Impacts On Chromatmentioning

confidence: 99%

Nuclear membrane diversity: underlying tissue-specific pathologies in disease?

Worman

Schirmer

2015

Current Opinion in Cell Biology

View full text Add to dashboard Cite

Human ‘laminopathy’ diseases result from mutations in genes encoding nuclear lamins or nuclear envelope (NE) transmembrane proteins (NETs). These diseases present a seeming paradox: the mutated proteins are widely expressed yet pathology is limited to specific tissues. New findings suggest tissue-specific pathologies arise because these widely expressed proteins act in various complexes that include tissue-specific components. Diverse mechanisms to achieve NE tissue-specificity include tissue-specific regulation of the expression, mRNA splicing, signaling, NE-localization and interactions of potentially hundreds of tissue-specific NETs. New findings suggest these NETs underlie tissue-specific NE roles in cytoskeletal mechanics, cell-cycle regulation, signaling, gene expression and genome organization. This view of the NE as ‘specialized’ in each cell type is important to understand the tissue-specific pathology of NE-linked diseases.

show abstract

BRD4 Short Isoform Interacts with RRP1B, SIPA1 and Components of the LINC Complex at the Inner Face of the Nuclear Membrane

Cited by 56 publications

References 58 publications

Suppression of SIPA-1 expression may reduce bladder cancer invasion and metastasis via the downregulation of E-cadherin and ZO-1

Suppression of SIPA-1 expression may reduce bladder cancer invasion and metastasis via the downregulation of E-cadherin and ZO-1

Chemical probes targeting epigenetic proteins: Applications beyond oncology

Nuclear membrane diversity: underlying tissue-specific pathologies in disease?

Contact Info

Product

Resources

About