Human LATS1 is a mitotic exit network kinase

Cancer Res. 2005 Aug 1;65(15):6568-75. doi: 10.1158/0008-5472.CAN-05-0862.

Abstract

The kinase LATS/WARTS is a tumor suppressor protein conserved in evolution, but its function at the molecular level is not well understood. We report here that human LATS1 interacts with MOB1A, a protein whose homologue in budding yeast associates with kinases involved in mitotic exit. This suggested that LATS1 may be a component of the previously uncharacterized mitotic exit network in higher eukaryotes. Indeed, moderate overexpression of human LATS1 in cells exposed to microtubule poisons facilitated mitotic exit, and this activity required MOB1A. Reciprocally, small interfering RNA-mediated suppression of LATS1 or MOB1A prolonged telophase, but had no effect on the length of the earlier phases of mitosis. A role of LATS1 in mitotic exit may explain its previously described abilities to induce G2 arrest and promote cytokinesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Centrosome / metabolism
  • HeLa Cells
  • Humans
  • Mitosis / physiology*
  • Molecular Sequence Data
  • Osteosarcoma / enzymology
  • Osteosarcoma / pathology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / physiology*
  • Telophase / physiology
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • MOB1B protein, human
  • LATS1 protein, human
  • Protein Serine-Threonine Kinases