LAPSER1 is a putative cytokinetic tumor suppressor that shows the same centrosome and midbody subcellular localization pattern as p80 katanin

FASEB J. 2007 Jul;21(9):2086-100. doi: 10.1096/fj.06-7254com. Epub 2007 Mar 9.

Abstract

Prostate cancer is one of the most common cancers in men, with more than 500,000 new worldwide cases reported annually, resulting in 200,000 deaths of mainly older men in developed countries. Existing treatments have not proved very effective in managing prostate cancer, and continuing efforts therefore are ongoing to explore novel targets and strategies for future therapies. LAPSER1 has been identified as a candidate tumor suppressor gene in prostate cancer, but its true functions remain unknown. We report here that LAPSER1 colocalizes to the centrosomes and midbodies in mitotic cells with gamma-tubulin, MKLP1, and p80 katanin, and is involved in cytokinesis. Moreover, RNAi-mediated disruption of LAPSER1, which is accompanied by the mislocalization of p80 katanin, results in malformation of the central spindle. Significantly, the enhanced expression of LAPSER1 induces binucleation and renders the cells resistant to oncogenic transformation. In cells transformed by the v-Fps oncogene, overexpressed LAPSER1 induces abortive cytokinesis, followed by mitotic catastrophe in a p80 katanin-dependent manner. Cells that are rescued from this apoptotic pathway with Z-VAD-fmk display karyokinesis. These results suggest that LAPSER1 participates in cytokinesis by interacting with p80 katanin, the disruption of which may potentially cause genetic instability and cancer.

MeSH terms

  • Adenocarcinoma / pathology
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis
  • Bone Neoplasms / pathology
  • CHO Cells
  • Cell Line
  • Cell Line, Transformed
  • Cell Line, Tumor / chemistry
  • Cell Line, Tumor / ultrastructure
  • Cell Transformation, Viral
  • Centrosome / chemistry*
  • Centrosome / ultrastructure
  • Cricetinae
  • Cricetulus
  • Cytokinesis / physiology*
  • Fusion Proteins, gag-onc / physiology
  • Genes, Tumor Suppressor*
  • Humans
  • Katanin
  • Leucine Zippers
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Microtubule-Associated Proteins / analysis
  • Oncogene Protein p21(ras) / physiology
  • Oncogene Proteins v-abl / physiology
  • Osteosarcoma / pathology
  • Polyploidy
  • Prostatic Neoplasms / pathology
  • Protein Subunits
  • Protein-Tyrosine Kinases / physiology
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Rats
  • Recombinant Fusion Proteins / physiology
  • Spindle Apparatus / ultrastructure
  • Subcellular Fractions / chemistry
  • Tubulin / analysis
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*

Substances

  • Amino Acid Chloromethyl Ketones
  • Fusion Proteins, gag-onc
  • KIF23 protein, human
  • LAPSER1 protein, rat
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Oncogene Proteins v-abl
  • Protein Subunits
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Tubulin
  • Tumor Suppressor Proteins
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Protein-Tyrosine Kinases
  • v-fps oncogene protein, Fujinami sarcoma virus
  • Adenosine Triphosphatases
  • Oncogene Protein p21(ras)
  • Katanin