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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biochem+J
2017 ; 474
(17
): 2953-2976
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The AAA+ ATPase p97, a cellular multitool
#MMPMID28819009
Stach L
; Freemont PS
Biochem J
2017[Aug]; 474
(17
): 2953-2976
PMID28819009
show ga
The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is
essential to a wide range of cellular functions, including endoplasmic
reticulum-associated degradation, membrane fusion, NF-?B (nuclear factor
kappa-light-chain-enhancer of activated B cells) activation and
chromatin-associated processes, which are regulated by ubiquitination. p97 acts
downstream from ubiquitin signaling events and utilizes the energy from ATP
hydrolysis to extract its substrate proteins from cellular structures or
multiprotein complexes. A multitude of p97 cofactors have evolved which are
essential to p97 function. Ubiquitin-interacting domains and p97-binding domains
combine to form bi-functional cofactors, whose complexes with p97 enable the
enzyme to interact with a wide range of ubiquitinated substrates. A set of
mutations in p97 have been shown to cause the multisystem proteinopathy inclusion
body myopathy associated with Paget's disease of bone and frontotemporal
dementia. In addition, p97 inhibition has been identified as a promising approach
to provoke proteotoxic stress in tumors. In this review, we will describe the
cellular processes governed by p97, how the cofactors interact with both p97 and
its ubiquitinated substrates, p97 enzymology and the current status in developing
p97 inhibitors for cancer therapy.
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