ARID3B induces tumor necrosis factor alpha mediated apoptosis while a novel ARID3B splice form does not induce cell death.
ARID3B induces tumor necrosis factor alpha mediated apoptosis while a novel ARID3B splice form does not induce cell death.
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DOI：
10.1371/journal.pone.0042159
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cowden Dahl KD
中科院分区：
文献类型：
--
作者：
Joseph S;Deneke VE;Cowden Dahl KD
选择性剪接在许多癌症中是常见的。选择性剪接与癌细胞凋亡和化疗耐药性的降低有关。我们以前证明，ARID 3B，一个AT丰富的DNA结合蛋白的相互作用域（ARID）家族的成员，在卵巢癌中过表达。因此，我们想要评估ARID 3B剪接形式对细胞活力的影响。我们鉴定了ARID 3B基因的新剪接形式（命名为ARID 3B Sh），其缺乏全长同种型（ARID 3B Fl）中存在的C末端外显子5-9。ARID 3B Fl在多种癌细胞系中表达。ARID 3B Sh的表达因细胞类型而异，但在大多数卵巢癌细胞系中高度表达。ARID 3B通过PEA 3转录因子由表皮生长因子受体（EGFR）信号传导适度地转录激活。我们进一步发现，ARID 3B Fl主要是核的，但也存在于质膜和胞质溶胶中。内源性ARID 3B Sh存在于核组分中，然而，当过表达时，ARID 3B Sh在胞质溶胶和膜组分中积累。这些异构体的差异定位表明它们具有不同的功能。重要的是，ARID 3B Fl过表达导致促凋亡BIM的上调并诱导肿瘤坏死因子α（TNFα）和TNF相关凋亡诱导配体（TRAIL）诱导的细胞死亡。ARID 3B Fl诱导的基因包括TNFα、TRAIL、TRADD、TNF-R2、Caspase 10和Caspase 7。有趣的是，ARID 3B Sh不诱导这些基因的凋亡或表达。ARID 3B Fl诱导死亡受体介导的细胞凋亡，而新的剪接形式ARID 3B Sh不诱导细胞死亡。因此，ARID 3B的选择性剪接形式可能在卵巢癌进展中发挥不同的作用。
Alternative splicing is a common occurrence in many cancers. Alternative splicing is linked with decreased apoptosis and chemoresistance in cancer cells. We previously demonstrated that ARID3B, a member of the AT-rich interactive domain (ARID) family of DNA binding proteins, is overexpressed in ovarian cancer. Therefore we wanted to assess the effect of ARID3B splice forms on cell viability. We identified a novel splice form of the ARID3B gene (designated as ARID3B Sh), which lacks the C-terminal exons 5–9 present in the full-length isoform (ARID3B Fl). ARID3B Fl is 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 modestly transcriptionally activated by epidermal growth factor receptor (EGFR) signaling through the PEA3 transcription factor. We further found that ARID3B Fl is predominantly nuclear but is also present at the plasma membrane and in the cytosol. 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 roles in ovarian cancer progression.
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影响因子：
11.2
作者：
Kobayashi, Kenichiro;Era, Takumi;Nishikawa, Shin-Ichi
通讯作者：
Nishikawa, Shin-Ichi
影响因子：
11.5
作者：
Nam, Eun Ji;Yoon, Heejei;Kim, Sunghoon
通讯作者：
Kim, Sunghoon
影响因子：
6.4
作者：
MOSER, TL;YOUNG, TN;STACK, MS
通讯作者：
STACK, MS
影响因子：
64.8
作者：
Gavathiotis, Evripidis;Suzuki, Motoshi;Davis, Marguerite L.;Pitter, Kenneth;Bird, Gregory H.;Katz, Samuel G.;Tu, Ho-Chou;Kim, Hyungjin;Cheng, Emily H. -Y.;Tjandra, Nico;Walensky, Loren D.
通讯作者：
Walensky, Loren D.
影响因子：
5.8
作者：
Sayers, TJ;Murphy, WJ
通讯作者：
Murphy, WJ