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演者: Hironori Funabiki博士

The Rockferor University&s_comma; New York&s_comma; USA

演題:Mechanism of Mitotic Aurora B Activation Stimulated

by Chromatin and Microtubules

日時:12月 10日 (月) 14 :00~15:00

場所:東京大学分子細胞生物学研究所総合研 究棟2階会議室

A number of essential mitotic events are controlled by the chromosomal passenger complex (CPC)&s_comma; which consists of Incenp&s_comma; Survivin&s_comma; Dasra A or B (also known as Borealin)&s_comma; and the kinase Aurora B. The CPC shows a dynamic intracellular localization patterns during mitosis: it is localized to chromosomes&s_comma; particularly enriched on innercentromeric heterochromatin from prophase to metaphase&s_comma; but in anaphase it is delocalized from centromeres and relocalized to spindle midzone. At these different locations&s_comma; it is thought that the CPC executes distinct function. However&s_comma; it remains unknown how this differential localization and activation of the CPC is regulated. Previously&s_comma; we have shown that both chromatin and stabilized microtubules can stimulate the Aurora B-dependent phosphorylation of Op18 and histone H3 in Xenopus egg extracts. Chromatin-induced spindle assembly in egg extracts depends on the coupled chromosome localization and activation of the Aurora B pathway. This coupling is normally mediated by Dasra&s_comma; Survivin and N-terminal Incenp&s_comma; which act together to locate the CPC to chromosomes. However&s_comma; this coupling can be bypassed by forced clustering of the CPC using anti-Incenp antibodies. Therefore&s_comma; we suggest that chromatin activates Aurora B by clustering. By contrast&s_comma; Dasra and Survivin are not required for microtubule-induced activation of the Aurora B pathway. We will discuss the mechanisms by which chromatin and microtubule differentially regulate Aurora B activity&s_comma; and the biological significance of positive feedback between Aurora B and microtubules during spindle assembly.

世話人:東大分生研・染色体動態研究分野 渡邊嘉典 (内21466)