First Author | McPherson JP | Year | 2004 |
Journal | EMBO J | Volume | 23 |
Issue | 18 | Pages | 3677-88 |
PubMed ID | 15343267 | Mgi Jnum | J:93191 |
Mgi Id | MGI:3056218 | Doi | 10.1038/sj.emboj.7600371 |
Citation | McPherson JP, et al. (2004) Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J 23(18):3677-88 |
abstractText | 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. |