Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability.
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.
Ota
Takahide
T
Division of Cancer Research, Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan.
Suto
Shiho
S
Katayama
Hiroshi
H
Han
Zhen-Bo
ZB
Suzuki
Fumio
F
Maeda
Masayo
M
Tanino
Mikio
M
Terada
Yasuhiko
Y
Tatsuka
Masaaki
M
D000782:Aneuploidy; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D014162:Transfection
D006657:Histones; D011494:Protein Kinases; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases