Increased mitotic phosphorylation of histone H3 attributable to AIM-1/aurora-B overexpression contributes to chromosome number instability

Takahide Ota, Shiho Suto, Hiroshi Katayama, Zhen Bo Han, Fumio Suzuki, Masayo Maeda, Mikio Tanino, Yasuhiko Terada, Masaaki Tatsuka

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Abstract

Phosphorylation of histone H3 at Ser-10 is required for maintenance of proper chromosome dynamics during mitosis. AIM-1, a mammalian Ip11/aurora kinase involved in H3 phosphorylation, is transcriptionally overexpressed in many tumor cell lines. Increased expression of the AIM-1 gene has been observed in human colorectal tumors of advanced grade and stage. Here we report that forced exogenous overexpression of AIM-1 in Chinese hamster embryo cells causes increased mitotic Ser-10 phosphorylation with concomitant induction of lagging chromosomes during mitosis. Lagging chromosomes could also be induced by transfection with mutated histone H3 (S10E), which is thought to maintain Ser-10 in the phosphorylated state. In the present study, chromosome number instability and increased tumor invasiveness were noted in constitutively AIM-1-overexpressing cells in vivo. Increased mitotic Ser-10 phosphorylation was also observed in various colorectal tumor cells with high AIM-1 expression levels. These data suggest that increased H3 histone phosphorylation as a result of AIM-1 overexpression is a major precipitating factor of chromosome instability and, thus, may play a role in carcinogenesis.

Original languageEnglish
Pages (from-to)5168-5177
Number of pages10
JournalCancer Research
Volume62
Issue number18
Publication statusPublished - 2002 Sep 15

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ota, T., Suto, S., Katayama, H., Han, Z. B., Suzuki, F., Maeda, M., Tanino, M., Terada, Y., & Tatsuka, M. (2002). Increased mitotic phosphorylation of histone H3 attributable to AIM-1/aurora-B overexpression contributes to chromosome number instability. Cancer Research, 62(18), 5168-5177.