Download Investigation of the role of hydrogen peroxide throughout cell cycle

Investigation of the role of hydrogen peroxide throughout cell cycle using optical imaging
Dongmin Kang
Department of Life Science, Ewha Womans University, Seoul, Korea
Abstract
The intracellular concentration of H2O2 oscillates during the cell cycle, peaking at G2-M phase.
Requirement of H2O2 molecules for mitotic progression and the molecular mechanism by
which increased H2O2 molecules control mitotic progression are poorly understood. Proteins
associated with the centrosome play key roles in mitotic progression in mammalian cells. The
activity of Cdk1-opposing phosphatases at the centrosome must be inhibited during early
mitosis to prevent premature dephosphorylation of Cdh1—an activator of the ubiquitin ligase
APC/C—and the consequent premature degradation of mitotic activators. In this talk, we show
that reversible oxidative inactivation of centrosome-bound protein phosphatases such as
Cdc14B by H2O2 is likely responsible for this inhibition. Whereas the centrosome is shielded
from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI)
during interphase, the centrosome-associated PrxI is selectively inactivated through
phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and
facilitating inactivation of centrosome-bound phosphatase(s). Dephosphorylation of PrxI by
okadaic acid–sensitive phosphatases during late mitosis again shields the centrosome from
H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatase(s) at the organelle.