EVI1 oncoprotein expression and CtBP1-association oscillate through the cell cycle
Authors
Paredes, RobertoSchneider, Marion
Pearson, Stella
Teng, Hsian Yin
Kelly, James R
Pierce, Andrew
Somervaille, Tim C P
Whetton, Anthony D
Meyer, Stefan
Affiliation
Stem Cell and Leukaemia Proteomics Laboratory, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
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Aberrantly high expression of EVI1 in acute myeloid leukaemia (AML) is associated with poor prognosis. For targeted treatment of EVI1 overexpressing AML a more detailed understanding of aspects of spatiotemporal interaction dynamics of the EVI1 protein is important. EVI1 overexpressing SB1690CB AML cells were used for quantification and protein interaction studies of EVI1 and ?EVI1. Cells were cell cycle-synchronised by mimosine and nocodazole treatment and expression of EVI1 and related proteins assessed by western blot, immunoprecipitation and immunofluorescence. EVI1 protein levels oscillate through the cell cycle, and EVI1 is degraded partly by the proteasome complex. Both EVI1 and ?EVI1 interact with the co-repressor CtBP1 but dissociate from CtBP1 complexes during mitosis. Furthermore, a large fraction of EVI1, but not ?EVI1 or CtBP1, resides in the nuclear matrix. In conclusion, EVI1- protein levels and EVI1-CtBP1 interaction dynamics vary though the cell cycle and differ between EVI1 and ?EVI1. These data ad to the functional characterisation of the EVI1 protein in AML and will be important for the development of targeted therapeutic approaches for EVI1-driven AML.Citation
Paredes R, Schneider M, Pearson S, Teng HY, Kelly JR, Pierce A, et al. EVI1 oncoprotein expression and CtBP1-association oscillate through the cell cycle. Mol Biol Rep. 2020;47(10):8293-300.Journal
Molecular Biology ReportsDOI
10.1007/s11033-020-05829-1PubMed ID
32979164Additional Links
https://dx.doi.org/10.1007/s11033-020-05829-1Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1007/s11033-020-05829-1
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