Ran in Mitosis - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 131

XRHAMM

TPX2
NuMA

Aurora A BARD1/BRCA1

XMAP215

NUP98
RanGAP1/RanBP2

Rae1

Eg5/Kif11

HURP

(X)Kid XCTK2/HSET

NuSAP

Cdk11

Mel28

Fig. 7.2 The Ran system controls the activity of a variety of different factors required in spindle
formation. The majority of them dissociate from importins (see Fig. 7.1 ) and are shown in green .
They often cooperate with additional regulators of spindle formation that are not directly con-
trolled by importins or exportins and which are themselves not subject to control by the Ran
system ( black ). RanGTP promotes binding of the nuclear export receptor CRM1 to the RanGAP/
RanBP2 ( purple ) complex and promotes its functional association with kinetochores

215 kDa), one of the most potent MT stabilisers in the vertebrate cytoplasm, with
the MAP HURP (hepatoma upregulated protein), the tetrameric mitotic motor
protein Eg5/Kif11 and Aurora A kinase. Inhibition of HURP function by selective
partial immunodepletion from Xenopus egg extracts abolishes formation of this
complex. Under these conditions, RanGTP nucleates MTs, but the asters initially
assembled do not organise into pseudo-spindles (Koffa et al. 2006 ). Interestingly,
HURP is also regulated by RanGTP through direct binding to importin

. Its
complete immunodepletion strongly reduces RanGTP-mediated MT assembly
around chromatin beads (Casanova et al. 2008 ), and siRNA mediated depletion of
HURP from human cells weakens bundling and stabilisation of kinetochore
(K) fibres MTs (Koffa et al. 2006 ; Sillje et al. 2006 ) by modulation of the activity
of KIF18A, an MT depolymerising kinesin (Ye et al. 2011 ). Knock-down of the

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