Exon skipping in Mcl-1 results in a Bcl-2 homology domain 3 only gene product that promotes cell death
Exon skipping in Mcl-1 results in a Bcl-2 homology domain 3 only gene product that promotes cell death
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DOI：
10.1074/jbc.m909572199
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发表时间：
2000-07-21
影响因子：
4.8
通讯作者：
Whyte, MKB
中科院分区：
文献类型：
--
作者：
Bingle, CD;Craig, RW;Whyte, MKB
Mcl-1是Bcl-2家族的成员，其在转录和转录后受到调节，全长Mcl-1编码的基因产物的表达导致细胞存活增强。如本文所报道的，人类Mcl-1基因也可以进行差异剪接，产生内部缺失的死亡诱导基因产物Mcl-1（s/Delta TM）。而全长Mcl-1来自三个编码外显子（而不是Bcl-2和该家族的其他抗凋亡成员中存在的两个），Mcl-1（s/Delta TM）剪接变体来自第一和第三外显子的连接以及中心外显子的跳跃。由于跳过的外显子和下游阅读框的移位，Bcl-2同源结构域（BH 3）保持完整，而BH 1-、BH 2-和跨膜编码结构域则不完整。因此，Mcl-1（s/Delta TM）仅具有类似于BH 3的特征，是促凋亡Bcl-2家族成员，因此，发现其促进细胞死亡。除了各种其他类型的调节，Mcl-1基因似乎理想地设计用于产生Bcl-2样活力促进或如本文所报道的仅BH 3死亡诱导基因产物。
Mcl-1 is a member of the Bcl-2 family that is regulated transcriptionally and post-transcriptionally, with expression of the full-length Mcl-1-encoded gene product resulting in enhanced cell survival. As reported here, the human Mcl-1 gene can also undergo differential splicing, which yields an internally deleted, death-inducing gene product, Mcl-1(s/Delta TM) . Whereas full-length Mcl-1 derives from three coding exons (instead of the two present in Bcl-2 and other anti-apoptotic members of this family), the Mcl-1(s/Delta TM) splice variant results from the joining of the first and third exons with skipping of the central exon. Because of the skipped exon and a shift in the reading frame downstream, the Bcl-2 homology domain (BH3) remains intact, whereas the BH1-, BH2-, and transmembrane-encoding domains do not. Mcl-1(s/Delta TM) thus has features similar to BH3 only, pro-apoptotic Bcl-2 family members and, accordingly, was found to promote cell death. In addition to a variety of other types of regulation, the Mcl-1 gene appears ideally designed for the generation of either a Bcl-2-like viability promoting or, as reported here, a BH3 only death-inducing gene product.