| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 6, 3648-3655, February 7, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the The 97-kDa valosin-containing protein
(p97-VCP) plays a role in a wide variety of cellular activities, many
of which are regulated by the ubiquitin-proteasome (Ub-Pr)-mediated
degradation pathway. We previously demonstrated that VCP binds to
multi-ubiquitin chains and may act as a molecular chaperone that
targets the ubiquitinated substrates to the proteasome for degradation.
In this report, we show that although the ubiquitin chain-binding
activity, carried out by the N-terminal 200 residues (N domain), is
necessary for the degradation of proteasome substrates, it is not
sufficient. Using in vitro degradation assays, we
demonstrated that the entire VCP molecule, consisting of the N domain
and two ATPase domains D1 and D2, is required for mediating the Ub-Pr
degradation. The ATPase activity of VCP requires Mg2+, and
is stimulated by high temperature. Under optimal conditions, VCP
hydrolyzes ATP with a Km of ~0.33 mM
and a Vmax of ~0.52 nmol
Pi min
ATPase Activity of p97-Valosin-containing Protein (VCP)
D2 MEDIATES THE MAJOR ENZYME ACTIVITY, AND D1 CONTRIBUTES TO THE
HEAT-INDUCED ACTIVITY*
§,§¶
Basic Research Program, SAIC-Frederick,
§ Basic Research Laboratory, National Cancer Institute,
Frederick, Maryland 21702
1 µg1. At a
physiological temperature, mutation in D2 significantly inhibits the
ATPase activity, while that in D1 has little effect. Interestingly,
mutations in D1, but not D2, abolish the heat-stimulated ATPase
activity. Thus, we provide the first demonstration that the ATPase
activity of VCP is required for mediating the Ub-Pr degradation, that
D2 accounts for the major ATPase activity, and that D1 contributes to
the heat-induced activity.
*
This work has been supported with Federal funds from the
NCI, National Institutes of Health under Contract No. NO1-CO-56000. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organization imply
endorsement by the United States Government.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Nishikori, K. Yamanaka, T. Sakurai, M. Esaki, and T. Ogura p97 homologs from Caenorhabditis elegans, CDC-48.1 and CDC-48.2, suppress the aggregate formation of huntingtin exon1 containing expanded polyQ repeat Genes Cells, August 1, 2008; 13(8): 827 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kressler, D. Roser, B. Pertschy, and E. Hurt The AAA ATPase Rix7 powers progression of ribosome biogenesis by stripping Nsa1 from pre-60S particles J. Cell Biol., June 16, 2008; 181(6): 935 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Briggs, G. S. Baldwin, N. Miyata, H. Kondo, X. Zhang, and P. S. Freemont Analysis of Nucleotide Binding to P97 Reveals the Properties of a Tandem AAA Hexameric ATPase J. Biol. Chem., May 16, 2008; 283(20): 13745 - 13752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Park, D. M. Rancour, and S. Y. Bednarek Protein Domain-Domain Interactions and Requirements for the Negative Regulation of Arabidopsis CDC48/p97 by the Plant Ubiquitin Regulatory X (UBX) Domain-containing Protein, PUX1 J. Biol. Chem., February 23, 2007; 282(8): 5217 - 5224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G. Mimnaugh, W. Xu, M. Vos, X. Yuan, and L. Neckers Endoplasmic Reticulum Vacuolization and Valosin-Containing Protein Relocalization Result from Simultaneous Hsp90 Inhibition by Geldanamycin and Proteasome Inhibition by Velcade Mol. Cancer Res., September 1, 2006; 4(9): 667 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Oberdorf, E. J. Carlson, and W. R. Skach Uncoupling proteasome peptidase and ATPase activities results in cytosolic release of an ER polytopic protein J. Cell Sci., January 15, 2006; 119(2): 303 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gerega, B. Rockel, J. Peters, T. Tamura, W. Baumeister, and P. Zwickl VAT, the Thermoplasma Homolog of Mammalian p97/VCP, Is an N Domain-regulated Protein Unfoldase J. Biol. Chem., December 30, 2005; 280(52): 42856 - 42862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Noguchi, T. Takata, Y. Kimura, A. Manno, K. Murakami, M. Koike, H. Ohizumi, S. Hori, and A. Kakizuka ATPase Activity of p97/Valosin-containing Protein Is Regulated by Oxidative Modification of the Evolutionally Conserved Cysteine 522 Residue in Walker A Motif J. Biol. Chem., December 16, 2005; 280(50): 41332 - 41341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, C. Song, L. Irizarry, R. Dai, X. Zhang, and C.-C. H. Li Multifunctional Roles of the Conserved Arg Residues in the Second Region of Homology of p97/Valosin-containing Protein J. Biol. Chem., December 9, 2005; 280(49): 40515 - 40523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Uchiyama and H. Kondo p97/p47-Mediated Biogenesis of Golgi and ER J. Biochem., February 1, 2005; 137(2): 115 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Rancour, S. Park, S. D. Knight, and S. Y. Bednarek Plant UBX Domain-containing Protein 1, PUX1, Regulates the Oligomeric Structure and Activity of Arabidopsis CDC48 J. Biol. Chem., December 24, 2004; 279(52): 54264 - 54274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Bruderer, C. Brasseur, and H. H. Meyer The AAA ATPase p97/VCP Interacts with Its Alternative Co-factors, Ufd1-Npl4 and p47, through a Common Bipartite Binding Mechanism J. Biol. Chem., November 26, 2004; 279(48): 49609 - 49616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dalal, M. F. N. Rosser, D. M. Cyr, and P. I. Hanson Distinct Roles for the AAA ATPases NSF and p97 in the Secretory Pathway Mol. Biol. Cell, February 1, 2004; 15(2): 637 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, C. Song, X. Yang, and C.-C. H. Li D1 Ring Is Stable and Nucleotide-independent, whereas D2 Ring Undergoes Major Conformational Changes during the ATPase Cycle of p97-VCP J. Biol. Chem., August 29, 2003; 278(35): 32784 - 32793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, H. H. Meyer, and T. A. Rapoport Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains J. Cell Biol., July 7, 2003; 162(1): 71 - 84. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
