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Vol. 16, No. 13, pp. 1640-1658, July 1, 2002
Department of Molecular Biology and the Diabetes Unit and Medical
Services, Massachusetts General Hospital, and the Department of
Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA
The protein kinase NIMA is an indispensable pleiotropic regulator of
mitotic progression in Aspergillus. Although several mammalian
NIMA-like kinases (Neks) are known, none appears to have the broad
importance for mitotic regulation attributed to NIMA. Nercc1 is a new
NIMA-like kinase that regulates chromosome alignment and segregation in
mitosis. Its NIMA-like catalytic domain is followed by a noncatalytic
tail containing seven repeats homologous to those of the Ran GEF, RCC1,
a Ser/Thr/Pro-rich segment, and a coiled-coil domain. Nercc1 binds to
another NIMA-like kinase, Nek6, and also binds specifically to the Ran
GTPase through both its catalytic and its RCC1-like domains, preferring
RanGDP in vivo. Nercc1 exists as a homooligomer and can autoactivate in vitro by autophosphorylation. Nercc1 is a cytoplasmic protein that is
activated during mitosis and is avidly phosphorylated by active
p34Cdc2. Microinjection of anti-Nercc1 antibodies in prophase
results in spindle abnormalities and/or chromosomal misalignment. In
Ptk2 cells the outcome is prometaphase arrest or aberrant chromosome segregation and aneuploidy, whereas in CFPAC-1 cells prolonged arrest
in prometaphase is the usual response. Nercc1 and its partner Nek6
represent a new signaling pathway that regulates mitotic progression.
[Key Words: NIMA; NEK; Ran; RCC1; cdc2/MPF; mitosis]
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