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Oncogenic role of nuclear accumulated Aurora‐A
Author(s) -
Tatsuka Masaaki,
Sato Sunao,
Kanda Akifumi,
Miki Tomoharu,
Kamata Nobuyuki,
Kitajima Shojiro,
Kudo Yasusei,
Takata Takashi
Publication year - 2009
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20525
Subject(s) - biology , nuclear localization sequence , nuclear protein , cancer cell , microbiology and biotechnology , cell nucleus , nuclear transport , cytoplasm , cancer research , cancer , gene , genetics , transcription factor
Abstract Aurora‐A, also known as Aik, BTAK, or STK15, is a centrosomal serine/threonine protein kinase, which is proto‐oncogenic and is overexpressed in a wide range of human cancers. Besides gene amplification and mRNA overexpression, proteolytic resistance mechanisms are thought to contribute to overexpression of Aurora‐A. However, it is not yet clear how overexpressed Aurora‐A affects the expression of transformed phenotype. Here, we found that nuclear accumulation of Aurora‐A was critical for transformation activity. Cellular protein fractionation experiments and immunoblot analysis demonstrated a predominance of Aurora‐A in the nuclear soluble fraction in head and neck cancer cells. Indirect immunofluorescence using confocal laser microscopy confirmed nuclear Aurora‐A in head and neck cancer cells, while most oral keratinocytes exhibited only centrosomal localization. The expression of nuclear export signal‐fused Aurora‐A demonstrated that the oncogenic transformation activity was lost on disruption of the nuclear localization. Thus, the cytoplasmic localization of overexpressed Aurora‐A previously demonstrated by immunohistochemical analysis is not likely to correspond to that in intact cancer cells. This study identifies an alternative mode of Aurora‐A overexpression in cancer, through nuclear rather than cytoplasmic functions. We suggest that substrates of Aurora‐A in the cell nuclear soluble fraction can represent a novel therapeutic target for cancer. © 2009 Wiley‐Liss, Inc.