Human homologue of Drosophila lats, LATS1, negatively regulate growth by inducing G(2)/M arrest or apoptosis

Oncogene. 2001 Oct 4;20(45):6516-23. doi: 10.1038/sj.onc.1204817.

Abstract

The lats gene encodes a family of proteins conserved from insects to humans. Drosophila carrying lats mutant cells or mice deficient for Lats1 develop tumors in various tissues. The mammalian LATS1 protein was previously shown to bind to CDC2, suggesting that LATS1 may modulate G(2)/M cell cycle progression by affecting CDC2 activity. In this study, we introduced human LATS1 into LATS(-/-) MEF cells by adenovirus-mediated gene transfer. Overexpression of LATS1 causes G(2)/M arrest through inhibition of CDC2 kinase activity. Furthermore, overexpression of LATS1 significantly suppressed the human tumor cell growth in vitro and tumorigenicity in vivo by inducing either cell cycle arrest in G(2)/M or apoptosis. These observations suggest that LATS1 is a potent growth suppressor and, like other tumor suppressors, it suppresses growth by inducing cell cycle arrest or apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis*
  • CDC2 Protein Kinase / antagonists & inhibitors
  • Cell Division
  • Cells, Cultured
  • Cyclin B / metabolism
  • Drosophila
  • Drosophila Proteins*
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • G2 Phase
  • Gene Deletion
  • Genetic Vectors
  • Humans
  • Mice
  • Mitosis
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • CycB protein, Drosophila
  • Cyclin B
  • Drosophila Proteins
  • Protein Kinases
  • LATS1 protein, human
  • Lats1 protein, mouse
  • wts protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase