Novel cell death by downregulation of eEF1A1 expression in tetraploids.
When duplicated sister chromatids are not properly compacted in mitosis, chromosomes are mis-segregated, inducing genetically unstable tetraploidy known to facilitate aneuploid malignancies. Here, we show that tetraploid cells produced by impaired chromosomal condensation are eliminated by a novel type of cell death different from caspase-dependent apoptosis. The cell death was associated with downregulation of eukaryotic translation elongation factor-1 alpha 1 (eEF1A1/EF-1alpha) expression in conjunction with accumulation of its mRNA in processing bodies (P bodies). Importantly, expression of exogenous eEF1A1 was shown to inhibit the caspase-independent cell death, and a similar cell death was observed after inducing the expression of short hairpin RNA specific for eEF1A1. Furthermore, the number of spontaneously arising binucleated cells was indicated to increase several fold during 1- to 2-week cultivation after initiation of exogenous eEF1A expression. Taken together, the novel cell death machinery should help to eliminate abnormal tetraploid cells and inhibit tumorigenesis.
Kobayashi
Y
Y
Laboratory of Molecular and Cellular Biology, Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Yonehara
S
S
D000782:Aneuploidy; D000818:Animals; D041702:BALB 3T3 Cells; D001483:Base Sequence; D016466:CHO Cells; D016923:Cell Death; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism; D020090:Chromosome Segregation; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D020648:Peptide Elongation Factor 1 / Q000096:biosynthesis*; D011123:Polyploidy; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
C094814:EEF1A1 protein, human; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger