DNA-dependent protein kinase在細胞有絲分裂的功能(1/3)
Date Issued
2004-05-28
Date
2004-05-28
Author(s)
呂勝春
DOI
922320B002190
Abstract
Since its first description in 1990, DNA-PK catalytic subunit has been one of the most
attractive and intriguing molecules in the research field. The bulk of studies has
implicated its participation in a wide array of cellular functions, including DNA
damage repair, V(D)J recombination, DNA replication, cell-cycle checkpoint and
apoptosis. Nevertheless, the role and mode of action of DNA-PKcs in these
pathways still remain obscure, mainly because of its difficulty in manipulation, as
well as the lack of reagents for tracking the active molecule in vivo. In the course of
our study we raised several antibodies against different portions of DNA-PKcs, and
most importantly, antibodies that can recognize specifically phosphorylated
DNA-PKcs, which represents the active kinase in in vivo. These antibodies enable
us to describe for the first time the behavior of activated DNA-PKcs in physiological
conditions, as well as during cell cycle progression. We detected the presence of
phosphorylated DNA-PKcs on duplicated centrosomes, and described its positive role
in microtubule nucleation. Furthermore, we found that phosphorylated DNA-PKcs
localize to the prometaphase kinetochores to interact with the AuroraB complex,
modulating its kinase activity. These findings reveal unforeseen functions for
DNA-PKcs, and may offer the key to unravel new insights into cell
nuclear/cytoplasmic coordination and cell cycle progression checkpoints.
Subjects
DNA-PK
centrosome
kinetochore
AuroraB
cell cycle progression
Publisher
臺北市：國立臺灣大學醫學院分子醫學研究所
Type
journal article
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