4.6 Article

The serine 2481-autophosphorylated form of mammalian Target Of Rapamycin (mTOR) is localized to midzone and midbody in dividing cancer cells

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.01.153

Keywords

mTOR; Cell cycle; Mitosis; Cytokinesis; Chromosomal passenger protein; Cancer

Funding

  1. (Ministerio de Sanidad y Consumo, Fondo de Investigacion Sanitaria - FIS, Spain) [CD08/00283]
  2. Susan G. Komen Breast Cancer Foundation (Texas, USA) [BCTR0600894]
  3. Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo, Fondo de Investigacion Sanitaria - FIS, Spain) [CP05-00090, PI06-0778, RD06-0020-0028]
  4. Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC, Spain)

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Using a high-resolution, automated confocal high-content imaging system, we investigated the sub-cellular localization of the Serine 2481-autophosphorylated form of mTOR (PP-mTOR(Ser2481)) during mitosis and cytokinesis in human cancer cells. PP-mTOR(Ser2481) exhibited a punctate nuclear distribution in interphase cancer cells, with the number of PP-mTOR(Ser2481) nuclear speckles positively relating with the proliferative capacity of cancer cells. PP-mTOR(Ser2481) expression dynamically rearranged within the cytoplasm in a close association near and between separating chromosomes during early stages of mitosis. Towards the end of anaphase and in telophase, PP-mTOR(Ser2481) drastically focused on the midzone and ultimately in the centre of the midbody at the presumptive cleavage furrow. In cells at cytokinesis, PP-mTOR(Ser2481) appeared as a doublet facing each other at the apical ends of two daughter cells. Three-dimensional analysis confirmed that PP-mTOR(Ser2481) positioned at a ring structure wrapped round by microtubule bundles to connect daughter cells. These results reveal for the first time that PP-mTOR(Ser2481) may be unexpectedly involved in the terminal stages of cytokinesis. (C) 2009 Elsevier Inc. All rights reserved.

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