EVI1 oncoprotein expression and CtBP1-association oscillate through the cell cycle
Teng, Hsiang Yin
Kelly, James R.
Somervaille, Tim C. P.
Whetton, Anthony D.
Meyer, Stefan; orcid: 0000-0002-2283-3690; email: email@example.com
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AbstractAbstract: 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 ΔEVI1. 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 ΔEVI1 interact with the co-repressor CtBP1 but dissociate from CtBP1 complexes during mitosis. Furthermore, a large fraction of EVI1, but not ΔEVI1 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 ΔEVI1. 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.
CitationMolecular Biology Reports, volume 47, issue 10, page 8293-8300
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2020-06-18, registration 2020-09-07, accepted 2020-09-07, pub-electronic 2020-09-26, online 2020-09-26, pub-print 2020-10
Publication status: Published
Funder: Bloodwise; doi: http://dx.doi.org/10.13039/501100007903; Grant(s): 150380, 10037, 19007
Funder: Kay Kendall Leukaemia Fund; doi: http://dx.doi.org/10.13039/501100000402; Grant(s): 792
Funder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289; Grant(s): C18601/A5901, C5759/A20971
Funder: Children's Cancer and Leukaemia Group; doi: http://dx.doi.org/10.13039/100011692; Grant(s): Toti Worboys Leukaemia Project
Funder: University of Manchester