MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair

Biochemical and Biophysical Research Communications
Shogo KojimaKeizo Takenaga

Abstract

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.

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Citations

Apr 14, 2010·Molecular and Cellular Biology·Daniel P StewartJoseph T Opferman
Oct 3, 2012·Trends in Cell Biology·Rhonda M Perciavalle, Joseph T Opferman
Nov 19, 2011·Biochimica Et Biophysica Acta·Brian C GeyerHermona Soreq
Apr 23, 2015·BMC Genomics·Lindsay M ReynoldsYongmei Liu
Dec 14, 2017·Nature Communications·Luisa VigevaniJuan Valcárcel

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