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PMID: 15343267 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 23 ·No. 18 ·2004-09-15 ·Pages 3677-88

McPherson JP, Tamblyn L, Elia A, Migon E, Shehabeldin A, Matysiak-Zablocki E, Lemmers B, Salmena L, Hakem A, Fish J, Kassam F, Squire J, Bruneau BG, Hande MP, Hakem R

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.

MeSH Terms
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
Chemicals
Tumor Suppressor Proteins LATS1 protein, human LATS2 protein, human Protein Serine-Threonine Kinases
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
McPherson John Peter
Division of Cellular & Molecular Biology, Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Tamblyn Laura
Elia Andrew
Migon Eva
Shehabeldin Amro
Matysiak-Zablocki Elzbieta
Lemmers Bénédicte
Salmena Leonardo
Hakem Anne
Fish Jason
Kassam Farah
Squire Jeremy
Bruneau Benoit G
Hande M Prakash
Hakem Razqallah
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600371
Published
2004-09-15
Epub
2004-00-02
Pages
3677-88
Language
English
Region
England
NLM ID
8208664
PMCID
PMC517611
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600371 PMC Full Text View journal details
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