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

Autor: Takahide, Ota, Shiho, Suto, Hiroshi, Katayama, Zhen-Bo, Han, Fumio, Suzuki, Masayo, Maeda, Mikio, Tanino, Yasuhiko, Terada, Masaaki, Tatsuka
Rok vydání: 2002
Předmět:
Zdroj: Cancer research. 62(18)
ISSN: 0008-5472
Popis: Phosphorylation of histone H3 at Ser-10 is required for maintenance of properchromosome dynamics during mitosis. AIM-1, a mammalian Ipl1/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.
Databáze: OpenAIRE