Downregulation o fserine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells

富含丝氨酸/精氨酸的剪接因子 3 的下调诱导结肠癌细胞 G1 细胞周期停滞和凋亡

• 批准号: 23590943
• 负责人: TANAHASHI Toshihito
• 金额: $ 3.58万
• 依托单位: Kobe Pharmaceutical University (2012-2013)Kobe University (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590943/
• 关键词: 選択的スプライシング; RNA結合タンパク質; 大腸がん; マイクロアレイ; ＲＮＡ結合タンパク質; 細胞周期; アポトーシス; p53; RIP-Chip; 大腸癌

Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SRSF family that plays wide-ranging roles in gene expression. SRSF3 knockdown induced G1 arrest and apoptosis in colon cancer cells (HCT116). Pathway analysis of differentially expressed transcripts in SRSF3-silenced cells and mRNAs immunoprecipitated with overexpressed SRSF3 suggested that SRSF3 preferentially associated with G1/S checkpoint regulator mRNAs and regulated their expression. SRSF3 knockdown decreased mRNA and protein levels of cyclins (D1, D3, and E1), E2F1, and E2F7. SRSF3 knockdown caused skipping of 81 nucleotides of the hipk2 exon 8. Resultant HIPK2 isoform partially lacking the E3 ubiquitin ligase-binding site became resistant to proteasome digestion. Predominant expression of the splice variant by selective decomposition of full-length hipk2 mRNA as well as by SERF3 knockdown induced apoptosis in a variety of colon cancer cells expressing wild-type or mutated p53.

丝氨酸/精氨酸富含剪接因子3（SRSF3）是SRSF家族的成员，在基因表达中扮演着广泛的角色。 SRSF3敲低诱导结肠癌细胞中的G1停滞和凋亡（HCT116）。用过表达的SRSF3对SRSF3细胞和MRNA免疫沉淀中差异表达的转录本的途径分析表明，SRSF3优先与G1/S检查点调节剂mRNA相关并调节其表达。 SRSF3敲低降低了细胞周期蛋白（D1，D3和E1），E2F1和E2F7的mRNA和蛋白质水平。 SRSF3敲低导致HIPK2外显子8的81个核苷酸跳过。由E3泛素连接酶结合位点部分缺乏结果，因此对蛋白酶体消化有抵抗力。通过选择性分解全长Hipk2 mRNA以及通过SERF3敲低的选择性分解，在多种表达野生型或突变p53的结肠癌细胞中诱导了凋亡。

项目成果

Hu antigen R (huR) functions as an alternative pre-mRNA splicing enhancer of transformer 2-beta (Tra2beta) on exon definition under oxidative stress

Hu 抗原 R (huR) 在氧化应激下作为 Transformer 2-beta (Tra2beta) 外显子定义的替代前 mRNA 剪接增强子

• 发表时间: 2011
• 作者: Masuda K;Yamagishi N;Kurokawa K;Satake Y;Kajita K;Akaike Y;Honda M;Nishida K;Kuwano Y;Tanahashi T;Rokutan K.
• 通讯作者: Rokutan K.

Premature stop codon-containing tra2beta4 mRNA isoform regulates cellular senescence

含有过早终止密码子的 tra2beta4 mRNA 亚型调节细胞衰老

• 发表时间: 2011
• 作者: Kajita K;Kuwano Y;Masuda K;Yamagishi N;Kurokawa K;Satake Y;Akaike Y;Honda M;Tanahashi T;Rokutan K
• 通讯作者: Rokutan K

Serine/arginine-rich splicing factor 3 (SRSF3) regulates G1/S checkpoint and p53-dependent apoptosis

富含丝氨酸/精氨酸的剪接因子 3 (SRSF3) 调节 G1/S 检查点和 p53 依赖性细胞凋亡

• 发表时间: 2011
• 作者: Kurokawa K;Akaike Y;Kajita K;Yamagishi N;Satake Y;Honda M;Nishida K;Kuwano Y;Masuda K;Tanahashi T;Rokutan K
• 通讯作者: Rokutan K

酸化ストレスと選択的スプライシングのクロストーク

氧化应激和选择性剪接之间的串扰

• 发表时间: 2011
• 作者: 棚橋俊仁;黒川憲;六反一仁
• 通讯作者: 六反一仁

Transfomer-2beta regulates apoptosis through post-transcriptional regulation of bcl-2

Transfomer-2beta 通过 bcl-2 转录后调节调节细胞凋亡

• 发表时间: 2011
• 作者: Kuwano Y;Kajita K;Satake Y;Kurokawa K;Yamagishi N;Akaike Y;Honda M;Nishida K;Masuda K;Tanahashi T;Rokutan K
• 通讯作者: Rokutan K