Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity.

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.
Authors	John Peter McPherson, Laura Tamblyn, Andrew Elia, Eva Migon, Amro Shehabeldin, Elzbieta Matysiak-Zablocki, Bénédicte Lemmers, Leonardo Salmena, Anne Hakem, Jason Fish, Farah Kassam, Jeremy Squire, Benoit G Bruneau, M Prakash Hande, Razqallah Hakem
Journal	The EMBO journal (EMBO J) Vol. 23 Issue 18 Pg. 3677-88 (Sep 15 2004) ISSN: 0261-4189 [Print] England
PMID	15343267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Tumor Suppressor Proteins LATS1 protein, human LATS2 protein, human Protein Serine-Threonine Kinases
Topics	Animals Apoptosis Cell Lineage Cell Proliferation Centrosome (physiology) Cytokinesis Female Fibroblasts (physiology) Gene Amplification Genes, Lethal Genomic Instability Male Mesoderm (metabolism) Mice (embryology) Mice, Inbred C57BL Mitosis Protein Serine-Threonine Kinases (genetics, physiology) Spindle Apparatus Tumor Suppressor Proteins (genetics, physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!