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|Title:||Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity|
|Source:||McPherson, J.P., Tamblyn, L., Elia, A., Migon, E., Shehabeldin, A., Matysiak-Zablocki, E., Lemmers, B., Salmena, L., Hakem, A., Fish, J., Kassam, F., Squire, J., Bruneau, B.G., Hande, M.P., Hakem, R. (2004-09-15). Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO Journal 23 (18) : 3677-3688. ScholarBank@NUS Repository. https://doi.org/10.1038/sj.emboj.7600371|
|Abstract:||The Drosophila melanogaster warts/lats tumour suppressor has two mammalian counterparts LATS1/Warts-1 and LATS2/Kpm. Here, we show that mammalian Lats orthologues exhibit distinct expression profiles according to germ cell layer origin. Lats2-/- embryos show overgrowth in restricted tissues of mesodermal lineage; however, lethality ultimately ensues on or before embryonic day 12.5 preceded by defective proliferation. Lats2-/- mouse embryonic fibroblasts (MEFs) acquire growth advantages and display a profound defect in contact inhibition of growth, yet exhibit defective cytokinesis. Lats2-/- embryos and MEFs display centrosome amplification and genomic instability. Lats2 localizes to centrosomes and overexpression of Lats2 suppresses centrosome overduplication induced in wild-type MEFs and reverses centrosome amplification inherent in Lats2-/- MEFs. These findings indicate an essential role of Lats2 in the integrity of processes that govern centrosome duplication, maintenance of mitotic fidelity and genomic stability.|
|Source Title:||EMBO Journal|
|Appears in Collections:||Staff Publications|
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