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Vol 56(2022) N 6 p. 1036-1045; DOI 10.1134/S0026893322060061 Full Text

D.E. Demin1*, E.M. Stasevich2, M.M. Murashko1, E.A. Tkachenko1,3, A.N. Uvarova2,3, A.M. Schwartz2,4

Full and D-Box-Deficient PTTG1 Isoforms: Effects on Cell Proliferation

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
3Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234 Russia
4Moscow Institute of Physics and Technology, Dolgoprudny, Moscow oblast, 141701 Russia

*denis.demin@phystech.edu
Received - 2022-06-15; Revised - 2022-07-03; Accepted - 2022-07-05

Human securin (PTTG1) is a protooncogene whose expression is elevated in many types of malignant cells. We previously discovered a minor short isoform of securin lacking exons 3 and 4. The missing exons encode the main recognition site (D-box) of the anaphase-promoting complex (APC/C). We show that these two PTTG1 isoforms have different effects on transcription. Here, we have studied the effects of overexpression and selective knockdown of the short and complete securin isoforms on cell proliferation using the xCELLigence system. Notably, selective knockdown of the short isoform mRNA led to a dramatic decrease in cell growth, while overexpression of both isoforms accelerated cell growth. To search for genes with alternative isoforms similar to securin, we analyzed the GENCODE database and found that 54 of 128 genes with a PTTG1-like set of APC/C recognition sites have known isoforms without the D-box. Overall, the data obtained indicate the existence of a new class of alternative isoforms and reinstates the importance of minor isoforms.

PTTG1, securin, minor isoform, oncogene, D-box, cell proliferation



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