MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair.
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.
Kojima
Shogo
S
Laboratory of Cancer Metastasis, Chiba Cancer Research Institute, Chuoh-ku, Chiba 260-8717, Japan.
Hyakutake
Akira
A
Koshikawa
Nobuko
N
Nakagawara
Akira
A
Takenaga
Keizo
K
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D055550:Protein Stability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing
D018076:DNA, Complementary; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2