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LAPSER1 is a putative cytokinetic tumor suppressor that shows the same centrosome and midbody subcellular localization pattern as p80 katanin
Author(s) -
Sudo Haruka,
Maru Yoshiro
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7254com
Subject(s) - centrosome , cytokinesis , midbody , mitosis , biology , microbiology and biotechnology , microtubule , cancer research , suppressor , oncogene , cancer cell , cancer , cell cycle , cell , genetics , cell division
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 mid‐bodies in mitotic cells with γ‐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 onco‐genic 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 karyoki‐nesis. These results suggest that LAPSER1 participates in cytokinesis by interacting with p80 katanin, the disruption of which may potentially cause genetic instability and cancer.–Sudo, H., Maru, Y. LAPSER1 is a putative cytokinetic tumor suppressor that shows the same centrosome and midbody subcellular localization pattern as p80 katanin. FASEB J. 21, 2086–2100 (2007)