Alternative splicing is usually a common occurrence in many cancers. exons 5-9 present in the full-length isoform (ARID3B Fl). ARID3B Fl is usually expressed in a variety of cancer cell lines. Expression of ARID3B Sh varied by cell type but was highly expressed in most ovarian cancer lines. ARID3B is usually modestly transcriptionally activated by epidermal growth factor receptor (EGFR) signaling through the PEA3 transcription factor. We further found that ARID3B Fl is usually predominantly nuclear but is also present at the plasma membrane and in the cytosol. GLYX-13 Endogenous ARID3B Sh is present in nuclear fractions yet when overexpressed ARID3B Sh accumulates in the cytosol and membrane fractions. The differential localization of these isoforms suggests they have different functions. Importantly ARID3B Fl overexpression results in upregulation of pro-apoptotic BIM and induces Tumor Necrosis Factor alpha (TNFα) and TNF-related apoptosis inducing ligand (TRAIL) induced cell death. The ARID3B Fl-induced genes include TNFα TRAIL TRADD TNF-R2 Caspase 10 and Caspase 7. Interestingly ARID3B Sh does not induce apoptosis or expression of these genes. ARID3B Fl induces death receptor mediated apoptosis while the novel splice form ARID3B Sh does not induce cell death. Therefore alternative splice forms of ARID3B may play different functions in ovarian cancer progression. Introduction Ovarian cancer represents the most lethal gynecological malignant GLYX-13 disease in the United States. According to the American Cancer Society [1] if diagnosed at the localized stage the 5-12 months survival rate is usually 94%; however only 15% of all cases are detected at this stage. The majority SMOC1 of cases of ovarian cancer (62%) are diagnosed with distant metastases [1]. For these women the 5-12 months survival rate is usually 28% [1] therefore determining the unique genetic programming that drives ovarian cancer progression is usually key in diagnosing and treating this disease. We previously identified ARID3B as a target of miR-125a a microRNA that is under GLYX-13 expressed in ovarian cancer [2] [3] [4]. However the function of ARID3B is usually relatively unknown. ARID3B belongs to the ARID family of proteins. The ARID family of transcriptional regulators is usually a conserved group of DNA binding proteins that regulates gene expression [5] [6]. ARID proteins harbor a distinctive DNA-binding domain name the AT-rich interactive domain name (ARID). Proteins of this family have been implicated in regulation of cell cycle gene expression differentiation embryonic development chromatin-remodeling and transcriptional regulation [6] GLYX-13 [7] [8] [9]. is the third factor of the ARID3 subfamily. ARID3B is usually most similar to its paralogue ARID3A however ARID3B and ARID3A are not closely related outside of the ARID extended ARID and REKLES domains [5] [7] [8] [10]. translated ARID3B binds to the same region of DNA as ARID3A near the immunoglobulin heavy chain enhancer called a matrix attachment region. ARID3A is usually primarily expressed in B-lymphocytes in adults [8] [10] [11]. In contrast ARID3B is much more widely expressed in the adult and is particularly highly GLYX-13 expressed in stratified epithelium and secretory cells (data not shown). Unlike ARID3A which actively shuttles between the nucleus and cytoplasm ARID3B was shown to localize exclusively to the nucleus when overexpressed in B-cell lines and in Cos7 cells [10] [12]. ARID3B enhances the nuclear localization of ARID3A by interacting with its REKLES β domain GLYX-13 name [10]. REKLES β mediated ARID3A-ARID3B conversation blocks nucleocytoplasmic shuttling of ARID3A by interfering with the nuclear export activity [10]. However ARID3A is usually incapable of re-localizing ARID3B suggesting a dominant effect for ARID3B around the cellular localization of both proteins [10]. Thus ARID3B could be key regulator in ARID3A function by regulating cellular localization in B cells. Since ARID3B is usually expressed more broadly than ARID3A it likely has other functions than its regulation of ARID3A. is essential during embryonic development [13] [14] [15]. Deletion of in mice leads to embryonic lethality poor angiogenesis limb bud defects and craniofacial and cardiovascular malformations [13] [14] [15]. Aberrant expression of ARID3B is found in malignant tumors. ARID3B is usually expressed in human neuroblastoma cell lines and in stage IV neuroblastoma but not in stage I-III indicating a possible role in the progression of malignant.