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Regulation of mitosis and taxane response by Daxx and Rassf1

Giovinazzi, S ; Lindsay, C R ; Morozov, V M ; Escobar-Cabrera, E ; Summers, M K ; Han, H S ; McIntosh, L P ; Ishov, A M

Oncogene, 2012-01, Vol.31 (1), p.13-26 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Regulation of mitosis and taxane response by Daxx and Rassf1
Autor: Giovinazzi, S ; Lindsay, C R ; Morozov, V M ; Escobar-Cabrera, E ; Summers, M K ; Han, H S ; McIntosh, L P ; Ishov, A M
Assuntos: Adaptor Proteins, Signal Transducing - physiology ; Anaphase ; Animal models ; Animals ; Antimitotic agents ; Antineoplastic agents ; Antineoplastic Agents, Phytogenic - pharmacology ; Binding sites ; Breast cancer ; Breast Neoplasms - drug therapy ; Cell Cycle ; Cell Line, Tumor ; Chemotherapy ; Cyclin B ; Cyclin B1 - analysis ; Data processing ; Daxx protein ; Drug Resistance, Neoplasm ; Drug therapy ; Female ; Genes ; Genetic aspects ; Health aspects ; Humans ; Malignancy ; Mice ; Mitosis ; Mitosis - drug effects ; Nuclear Proteins - physiology ; Paclitaxel ; Paclitaxel - pharmacology ; Physiological aspects ; Proteins ; Stress ; taxanes ; Tumor Suppressor Proteins - chemistry ; Tumor Suppressor Proteins - physiology ; Tumors ; Ubiquitin-protein ligase ; Xenografts
É parte de: Oncogene, 2012-01, Vol.31 (1), p.13-26
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
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The authors contributed equally.
Descrição: Current theories suggest that mitotic checkpoint proteins are essential for proper cellular response to taxanes, a widely used family of chemotherapeutic compounds. We recently showed that absence or depletion of protein Daxx increases cellular taxol (paclitaxel) resistance-a common trait of patients diagnosed with several malignancies, including breast cancer. Further investigation of Daxx-mediated taxol response revealed that Daxx is important for the proper timing of mitosis progression and cyclin B stability. Daxx interacts with mitotic checkpoint protein RAS-association domain family protein 1 (Rassf1) and partially colocalizes with this protein during mitosis. Rassf1/Daxx depletion or expression of Daxx-binding domain of Rassf1 elevates cyclin B stability and increases taxol resistance in cells and mouse xenograft models. In breast cancer patients, we observed the inverse correlation between Daxx and clinical response to taxane-based chemotherapy. These data suggest that Daxx and Rassf1 define a mitotic stress checkpoint that enables cells to exit mitosis as micronucleated cells (and eventually die) when encountered with specific mitotic stress stimuli, including taxol. Surprisingly, depletion of Daxx or Rassf1 does not change the activity of E3 ubiquitin ligase anaphase promotion complex/C in in vitro settings, suggesting the necessity of mitotic cellular environment for proper activation of this checkpoint. Daxx and Rassf1 may become useful predictive markers for the proper selection of patients for taxane chemotherapy.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Regulation of mitosis and taxane response by Daxx and Rassf1

Giovinazzi, S ; Lindsay, C R ; Morozov, V M ; Escobar-Cabrera, E ; Summers, M K ; Han, H S ; McIntosh, L P ; Ishov, A M

England: Nature Publishing Group

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