Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes

被引：6

作者：

Pontifex, Carly S. ^{[1
]}

Zaman, Mashiat ^{[1
,2
,3
]}

Fanganiello, Roberto D. ^{[4
]}

Shutt, Timothy E. ^{[1
,2
,3
]}

Pfeffer, Gerald ^{[1
,2
,5
]}

机构：

[1] Univ Calgary, Hotchkiss Brain Inst, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada

[2] Univ Calgary, Alberta Child Hlth Res Inst, Cumming Sch Med, Dept Med Genet, Calgary, AB T2N 1N4, Canada

[3] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 1N4, Canada

[4] Univ Laval, Fac Sci & Engn, Quebec City, PQ G1V 0A6, Canada

[5] Heritage Med Res Bldg 155,3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 11期

关键词：

valosin-containing protein; multisystem proteinopathy; genetic diagnosis; genotype-phenotype correlation; autophagy; mitophagy; lysophagy; stress granules; ERAD; cell cycle control; DNA damage response; apoptosis; SUMOylation; ubiquitination; skeletal muscle; osteoclast; neuron; MITOCHONDRIAL QUALITY-CONTROL; ENDOPLASMIC-RETICULUM STRESS; DNA-REPLICATION TERMINATION; AAA-ATPASE; MULTISYSTEM PROTEINOPATHY; FRONTOTEMPORAL DEMENTIA; PAGET-DISEASE; DAMAGED MITOCHONDRIA; AUTOPHAGIC FLUX; REPAIR PATHWAY;

D O I：

10.3390/ijms25115633

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this review we examine the functionally diverse ATPase associated with various cellular activities (AAA-ATPase), valosin-containing protein (VCP/p97), its molecular functions, the mutational landscape of VCP and the phenotypic manifestation of VCP disease. VCP is crucial to a multitude of cellular functions including protein quality control, endoplasmic reticulum-associated degradation (ERAD), autophagy, mitophagy, lysophagy, stress granule formation and clearance, DNA replication and mitosis, DNA damage response including nucleotide excision repair, ATM- and ATR-mediated damage response, homologous repair and non-homologous end joining. VCP variants cause multisystem proteinopathy, and pathology can arise in several tissue types such as skeletal muscle, bone, brain, motor neurons, sensory neurons and possibly cardiac muscle, with the disease course being challenging to predict.

引用

页数：23

共 171 条

[1] Valosin-containing protein (VCP) mutations in sporadic amyotrophic lateral sclerosis [J].

Abramzon, Yevgeniya ;

Johnson, Janel O. ;

Scholz, Sonja W. ;

Taylor, J. P. ;

Brunetti, Maura ;

Calvo, Andrea ;

Mandrioli, Jessica ;

Benatar, Michael ;

Mora, Gabriele ;

Restagno, Gabriella ;

Chio, Adriano ;

Traynor, Bryan J. .

NEUROBIOLOGY OF AGING, 2012, 33 (09)

[2] The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks [J].

Acs, Klara ;

Luijsterburg, Martijn S. ;

Ackermann, Leena ;

Salomons, Florian A. ;

Hoppe, Thorsten ;

Dantuma, Nico P. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2011, 18 (12) :1345-U55

[3] Ventricular myocytes are not terminally differentiated in the adult mammalian heart [J].

Anversa, P ;

Kajstura, J .

CIRCULATION RESEARCH, 1998, 83 (01) :1-14

[4] VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle [J].

Arhzaouy, Khalid ;

Papadopoulos, Chrisovalantis ;

Schulze, Nina ;

Pittman, Sara K. ;

Meyer, Hemmo ;

Weihl, Conrad C. .

AUTOPHAGY, 2019, 15 (06) :1082-1099

[5] Pathological stress granules in Alzheimer's disease [J].

Ash, Peter E. A. ;

Vanderweyde, Tara E. ;

Youmans, Katherine L. ;

Apicco, Daniel J. ;

Wolozin, Benjamin .

BRAIN RESEARCH, 2014, 1584 :52-58

[6] VCP Associated Inclusion Body Myopathy and Paget Disease of Bone Knock-In Mouse Model Exhibits Tissue Pathology Typical of Human Disease [J].

Badadani, Mallikarjun ;

Nalbandian, Angele ;

Watts, Giles D. ;

Vesa, Jouni ;

Kitazawa, Masashi ;

Su, Hailing ;

Tanaja, Jasmin ;

Dec, Eric ;

Wallace, Douglas C. ;

Mukherjee, Jogeshwar ;

Caiozzo, Vincent ;

Warman, Matthew ;

Kimonis, Virginia E. .

PLOS ONE, 2010, 5 (10)

[7] Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels [J].

Bartolome, Fernando ;

Wu, Hsiu-Chuan ;

Burchell, Victoria S. ;

Preza, Elisavet ;

Wray, Selina ;

Mahoney, Colin J. ;

Fox, Nick C. ;

Calvo, Andrea ;

Canosa, Antonio ;

Moglia, Cristina ;

Mandrioli, Jessica ;

Chio, Adriano ;

Orrell, Richard W. ;

Houlden, Henry ;

Hardy, John ;

Abramov, Andrey Y. ;

Plun-Favreau, Helene .

NEURON, 2013, 78 (01) :57-64

[8] Specific mutations in the D1-D2 linker region of VCP/p97 enhance ATPase activity and confer resistance to VCP inhibitors [J].

Bastola, Prabhakar ;

Wang, Feng ;

Schaich, Matthew A. ;

Gan, Taiping ;

Freudenthal, Bret D. ;

Chou, Tsui-Fen ;

Chien, Jeremy .

CELL DEATH DISCOVERY, 2017, 3

[9] VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal [J].

Bastola, Prabhakar ;

Neums, Lisa ;

Schoenen, Frank J. ;

Chien, Jeremy .

MOLECULAR ONCOLOGY, 2016, 10 (10) :1559-1574

[10] IBMPFD Disease-Causing Mutant VCP/p97 Proteins Are Targets of Autophagic-Lysosomal Degradation [J].

Bayraktar, Oznur ;

Oral, Ozlem ;

Kocaturk, Nur Mehpare ;

Akkoc, Yunus ;

Eberhart, Karin ;

Kosar, Ali ;

Gozuacik, Devrim .

PLOS ONE, 2016, 11 (10)

← 1 2 3 4 5 6 7 8 9 10 →