UBXD7 Binds Multiple Ubiquitin Ligases and Implicates p97 in HIF1α Turnover
08/09/2008
p97 is an
ATP-dependent chaperone that plays an important role
in endoplasmic reticulum-associated degradation but
whose connections to turnover of soluble proteins
remain sparse. Binding of p97 to substrates is
mediated by cofactors that contain ubiquitin-binding
domains. We employed “network proteomics” to show
that p97 assembles with all of the 13 mammalian
UBX-domain proteins. The UBX proteins that bind
ubiquitin conjugates also interact with dozens of E3
ubiquitin ligases, only one of which had been
previously linked to p97. In particular, UBXD7 links
p97 to the ubiquitin ligase CUL2/VHL and its
substrate hypoxia-inducible factor 1α
(HIF1&alpha
. Depletion of p97 leads to
accumulation of endogenous HIF1α and increased
expression of a HIF1α target gene. The large
number of ubiquitin ligases found associated
with UBX proteins suggests that p97 plays a far
broader role than previously anticipated in the
global regulation of protein turnover.
Cell, Vol 134, 804-816, 05 September 2008
. Depletion of p97 leads to
accumulation of endogenous HIF1α and increased
expression of a HIF1α target gene. The large
number of ubiquitin ligases found associated
with UBX proteins suggests that p97 plays a far
broader role than previously anticipated in the
global regulation of protein turnover.
Cell, Vol 134, 804-816, 05 September 2008
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