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Polo-like kinase 1 phosphorylates and regulates Bcl-xL during pironetin-induced apoptosis

Oncogene volume 28, pages 107–116 (2009)Cite this article

Abstract

Bcl-xL, an anti-apoptotic Bcl-2 family member protein, contributes to the resistance against chemotherapies such as tubulin-binder treatment in many human tumors. Although Bcl-xL is phosphorylated after tubulin-binder treatment, the role of the phosphorylation and its responsible kinase(s) are poorly understood. Here, we identified Plk1 (polo-like kinase 1) as a Bcl-xL kinase. Same location of Bcl-xL and Plk1 was revealed by immunocytochemical analyses at M-phase in situ. Plk1 phosphorylates Bcl-xL in vitro, and we identified Plk1 phosphorylation sites in Bcl-xL. When all of these phosphorylation sites were substituted to alanines, the anti-apoptotic activity of the Bcl-xL mutant against the apoptosis induced by pironetin, but not against ultraviolet-induced apoptosis, was increased. These observations suggest that Plk1 is a regulator of Bcl-xL phosphorylation and controls the anti-apoptotic activity of Bcl-xL during pironetin-induced apoptosis.

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Acknowledgements

We thank Y Ichikawa and R Nakazawa (Bioarchitect Research Group, RIKEN) for the DNA sequencing, and I Kagawa, M Kumai, E Oka and F Sakai (Research Resources Center, RIKEN) for the peptide synthesis, phospho-Ser62-specific rabbit polyclonal antibody production and affinity purification. This study was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Chemical Biology Project (RIKEN). YT and ST are recipients of the Junior Research Associate fellowship of RIKEN.

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Authors and Affiliations

  1. Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN, Wako, Saitama, Japan,

    Y Tamura, S Simizu, M Muroi, S Takagi, M Kawatani, N Watanabe & H Osada

  2. Graduate School of Science and Engineering, Saitama University, Saitama, Japan

    Y Tamura, S Takagi & H Osada

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  1. Y Tamura
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  2. S Simizu
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  3. M Muroi
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  4. S Takagi
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  5. M Kawatani
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  7. H Osada
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Correspondence to H Osada.

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Tamura, Y., Simizu, S., Muroi, M. et al. Polo-like kinase 1 phosphorylates and regulates Bcl-xL during pironetin-induced apoptosis. Oncogene 28, 107–116 (2009). https://doi.org/10.1038/onc.2008.368

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