MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair.
MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair.
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DOI：
10.1016/j.bbrc.2009.11.086
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发表时间：
2010
影响因子：
3.1
通讯作者：
S. Kojima;Akira Hyakutake;N. Koshikawa;A. Nakagawara;K. Takenaga
中科院分区：
文献类型：
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作者：
S. Kojima;Akira Hyakutake;N. Koshikawa;A. Nakagawara;K. Takenaga
属于 BCL-2 家族的髓样细胞白血病-1 (MCL-1) 对于造血干细胞的生存至关重要。它在各种类型的癌症中表达上调并促进癌细胞转移。已知人类MCL-1基因经历差异剪接并产生编码抗凋亡MCL-1L、促凋亡MCL-1S和MCL-1ES的三种mRNA。然而，小鼠细胞中尚未报道 MCL-1 变异。我们在此报告了小鼠 Mcl-1 的一种新剪接变体 Mcl-1V，它在多种小鼠正常和肿瘤细胞系和组织中表达。全长 Mcl-1 和 Mcl-1V cDNA 的比较序列分析表明，Mcl-1V mRNA 是由非规范供体-受体对中 Mcl-1 基因的第一个编码外显子内的剪接产生的。 MCL-1V 在 MCL-1 的 N 末端区域内缺少 46 个氨基酸残基。它定位于线粒体，与 MCL-1 一样有效地抑制缺氧和抗癌药物诱导的细胞凋亡，并且在发生细胞凋亡的细胞中衰减速度比 MCL-1 慢。总的来说，我们的结果表明小鼠细胞普遍表达抗凋亡 MCL-1V，可能在线粒体细胞死亡中发挥作用。
Myeloid cell leukemia-1 (MCL-1) that belongs to BCL-2 family is essential for survival of hematopoietic stem cells. It is upregulated in various types of cancer and promotes cancer cell metastasis. It is known that human MCL-1 gene undergoes differential splicing and yields three mRNAs encoding antiapoptotic MCL-1L and proapoptotic MCL-1S and MCL-1ES. However, no MCL-1 variants have been reported in mouse cells. We report here a new splicing variant of mouse Mcl-1, Mcl-1V, that is expressed in a variety of mouse normal and tumor cell lines and tissues. Comparative sequence analysis of the full-length Mcl-1 and Mcl-1V cDNAs suggested that Mcl-1V mRNA results from splicing within the first coding exon of Mcl-1 gene at a non-canonical donor–acceptor pair. MCL-1V lacks 46 amino acid residues within the N-terminal region of MCL-1. It localizes in mitochondria and inhibits anoxia- and anticancer drug-induced apoptosis as potent as MCL-1, and decayed less rapidly than MCL-1 in the cells undergoing apoptosis. Collectively, our results show that mouse cells ubiquitously express antiapoptotic MCL-1V that may play a role in mitochondrial cell death.