Mitotic Regulation Research Laboratory
UNDERSTANDING MITOSIS
Cell proliferation is the basis for development of tissues and organs. During mitosis a cell divides in to two newly formed genetically identical cells. Our main research interest is understanding the regulation of cell division, focusing on an E3 ligase called the Anaphase Promoting Complex/Cyclosome (APC/C). Although its mechanism of action and its atomic structure are well studied, there are still some open questions. We are interested in the complex formed by the proteins MAD2L2-CDH1 and its inhibitory effect on APC/C activation. Understanding the MAD2L2 mechanism of action may help design and develop specific drugs for inhibiting APC/C in cancer cells.
In addition, MAD2L2 is over expressed in several types of cancer. We are exploring the link between APC/C dis-regulation and MAD2L2 expression in breast cancer cells, to try and identify early events that could cause abnormal mitosis.
RESEARCH
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Mapping MAD2L2-CDH1 interaction, Using Immunoprecipitation of various CDH1 and MAD2L2 mutants, are trying to map their interaction and study the effect on cell growth.
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Characterizing mitosis in triple negative breast cancer cell lines, expressing high levels of MAD2L2.
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Studying new partners of MAD2L2 and the their binding regulation.
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Developing a small molecule for inhibiting TLS pathway
We are experts in biochemistry and molecular cell biology. We use molecular genetics in order to understand basic questions regarding mitotic regulation.
Our group:
Philippa Jennifer Ayiku - PhD student
Sahar Mobshovitz - M.Sc student
Alumni
Nomi Barda (Pernicone), PhD
Liza Edelshtein, M.Sc
Reuven Eisenstein, M.Sc
Shira Grinshpon M.Sc
Mira Litvak M.Sc
Limor Peretz M.Sc
PUBLICATIONS
CDH1 binds MAD2L2 in a Rev1-like pattern
Nomi Pernicone , Shira Grinshpon Tamar Listovsky Biochemical and Biophysical Research Communications. 2020 531 (4), 566-572
doi: 10.1016/j.bbrc.2020.07.118
MDA-MB-157 Cell Line Presents High Levels of MAD2L2 and Dysregulated Mitosis.
Pernicone N, Peretz L, Grinshpon S, Listovsky T. Anticancer Res. 2020 Oct;40(10):5471-5480. doi: 10.21873/anticanres.14558.PMID: 32988869
Sequestration of CDH1 by MAD2L2 prevents premature APC/C activation prior to anaphase onset. Journal of Cell Biology. 2013 (1)87-100
Tamar Listovsky , Julian E Sale
doi: 10.1083/jcb.201302060
Disrupting the MAD2L2-Rev1 Complex Enhances Cell Death upon DNA Damage
N Pernicone, M Elias, I Onn, D Tobi, T Listovsky
Molecules 2022 27 (3), 636
https://doi.org/10.3390/molecules27030636
MAD2L2 Dimerization Is Not Essential for Mitotic Regulation
Barda, N., Ayiku, P. J., Bar-on, A., Movshovitz, S., & Listovsky, T.
Int. J. Mol. Sci 2024, 25, 11485, 1–14.
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REV7 has a dynamic adaptor region to accommodate small GTPase RAN/Shigella IpaB ligands, and its activity is regulated by the RanGTP/GDP switch.
Wang X, Pernicone N, Pertz L, Hua D, Zhang T, Listovsky T, Xie W.J Biol Chem. 2019 Oct 25;294(43):15733-15742. doi: 10.1074/jbc.RA119.010123.
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