{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nValosin‐containing protein (VCP), also known as p97, is an evolutionarily conserved AAA+ ATPase that functions as a central regulator of protein homeostasis. By recognizing and extracting ubiquitinated substrates from diverse cellular structures such as the endoplasmic reticulum, mitochondria, and chromatin, VCP facilitates their subsequent degradation via the proteasome or lysosome. In particular, VCP’s segregase activity is critical for dislocating misfolded proteins during ER‐associated degradation (ERAD) and for processing substrates marked by ubiquitination in multiple quality‐control pathways. These processes are underscored by studies showing VCP’s involvement in the retrotranslocation of ER clients, the regulation of transcription factor activation via ubiquitination‐dependent mechanisms, and the remodeling of protein complexes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in proteostasis, VCP is essential for maintaining organelle quality control and cellular stress responses. It governs key steps in autophagosome maturation and mitophagy—processes that ensure the removal of damaged mitochondria and other dysfunctional organelles—as well as the disassembly and clearance of stress granules and aberrant ribonucleoprotein complexes. Experimental inhibition or mutation of VCP disrupts these degradation pathways, leading to accumulation of nondegradative autophagic vacuoles, delayed turnover of damaged lysosomes, and altered stress granule dynamics, which in turn contribute to proteotoxic stress in disease models. These aspects of VCP function have been demonstrated in diverse cellular settings, ranging from tumor models treated with selective p97 inhibitors to studies of its role in lysosomal and mitochondrial quality control."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in protein and organelle quality control, VCP participates in the regulation of key cellular signaling pathways and is closely linked to several degenerative and neoplastic diseases. Its interactions with numerous cofactors modulate signaling cascades—ranging from NF‑κB activation and DNA damage repair via removal of inhibitory chromatin factors to the regulation of lipid droplet dynamics through caveolin trafficking—and alterations in its activity (often by pathogenic mutations) are associated with conditions such as amyotrophic lateral sclerosis, inclusion body myopathy, frontotemporal dementia, and certain forms of Charcot–Marie–Tooth disease. Furthermore, emerging evidence indicates that post‑translational modifications such as lysine methylation can fine‑tune VCP’s ATPase function, providing an additional regulatory layer that influences substrate processing and cellular stress responsiveness. Collectively, these studies demonstrate that VCP acts as an integrative hub in ubiquitin‐mediated degradation pathways and cellular quality control, with its dysfunction contributing to diverse human pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qiuyan Wang, Lianyun Li, Yihong Ye "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of p97-dependent protein degradation by Eeyarestatin I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M708347200"}], "href": "https://doi.org/10.1074/jbc.M708347200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18199748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18199748"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gabriela Alexandru, Johannes Graumann, Geoffrey T Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.06.048"}], "href": "https://doi.org/10.1016/j.cell.2008.06.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18775313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18775313"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wai Kwan Tang, Dongyang Li, Chou-chi Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201007013"}], "href": "https://doi.org/10.1083/jcb.201007013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21173115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21173115"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Alexandra Stolz, Wolfgang Hilt, Alexander Buchberger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cdc48: a power machine in protein degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Biochem Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tibs.2011.06.001"}], "href": "https://doi.org/10.1016/j.tibs.2011.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21741246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21741246"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hemmo Meyer, Monika Bug, Sebastian Bremer "}, {"type": "b", "children": [{"type": "t", "text": "Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2407"}], "href": "https://doi.org/10.1038/ncb2407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22298039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22298039"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Senthil K Radhakrishnan, Willem den Besten, Raymond J Deshaies "}, {"type": "b", "children": [{"type": "t", "text": "p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.01856"}], "href": "https://doi.org/10.7554/eLife.01856"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24448410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24448410"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jeong-Sun Ju, Rodrigo A Fuentealba, Sara E Miller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200908115"}], "href": "https://doi.org/10.1083/jcb.200908115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20008565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20008565"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Emilie Tresse, Florian A Salomons, Jouni Vesa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.6.2.11014"}], "href": "https://doi.org/10.4161/auto.6.2.11014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20104022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20104022"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "J Ross Buchan, Regina-Maria Kolaitis, J Paul Taylor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2013.05.037"}], "href": "https://doi.org/10.1016/j.cell.2013.05.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23791177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23791177"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "S J Seguin, F F Morelli, J Vinet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2014.103"}], "href": "https://doi.org/10.1038/cdd.2014.103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25034784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25034784"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hemmo Meyer, Conrad C Weihl "}, {"type": "b", "children": [{"type": "t", "text": "The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.093831"}], "href": "https://doi.org/10.1242/jcs.093831"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25146396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25146396"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Daniel J Anderson, Ronan Le Moigne, Stevan Djakovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2015.10.002"}], "href": "https://doi.org/10.1016/j.ccell.2015.10.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26555175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26555175"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Chrisovalantis Papadopoulos, Philipp Kirchner, Monika Bug, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201695148"}], "href": "https://doi.org/10.15252/embj.201695148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27753622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27753622"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Gian-Luca McLelland, Thomas Goiran, Wei Yi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.abf6548"}], "href": "https://doi.org/10.1126/science.abf6548"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34739333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34739333"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Tatsuya Asai, Yasuhiko Tomita, Shin-ichi Nakatsuka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VCP (p97) regulates NFkappaB signaling pathway, which is important for metastasis of osteosarcoma cell line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Jpn J Cancer Res (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1349-7006.2002.tb02172.x"}], "href": "https://doi.org/10.1111/j.1349-7006.2002.tb02172.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11927012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11927012"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Taeko Kobayashi, Keiko Tanaka, Kiyoshi Inoue, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2003.06.068"}], "href": "https://doi.org/10.1200/JCO.2003.06.068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12560433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12560433"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ellen W Doss-Pepe, Edward S Stenroos, William G Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.18.6469-6483.2003"}], "href": "https://doi.org/10.1128/MCB.23.18.6469-6483.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12944474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12944474"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Mark S Forman, Ian R Mackenzie, Nigel J Cairns, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuropathol Exp Neurol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00005072-200606000-00005"}], "href": "https://doi.org/10.1097/00005072-200606000-00005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16783167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16783167"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Cezary Wójcik, Maga Rowicka, Andrzej Kudlicki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Valosin-containing protein (p97) is a regulator of endoplasmic reticulum stress and of the degradation of N-end rule and ubiquitin-fusion degradation pathway substrates in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e06-05-0432"}], "href": "https://doi.org/10.1091/mbc.e06-05-0432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16914519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16914519"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "G D J Watts, D Thomasova, S K Ramdeen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2007.00887.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2007.00887.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17935506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17935506"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Dalia Halawani, Andréa C LeBlanc, Isabelle Rouiller, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2009.09.016"}], "href": "https://doi.org/10.1016/j.molcel.2009.09.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19818707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19818707"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Precious J Lim, Rebecca Danner, Jing Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquilin and p97/VCP bind erasin, forming a complex involved in ERAD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200903024"}], "href": "https://doi.org/10.1083/jcb.200903024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19822669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19822669"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Janel O Johnson, Jessica Mandrioli, Michael Benatar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing reveals VCP mutations as a cause of familial ALS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2010.11.036"}], "href": "https://doi.org/10.1016/j.neuron.2010.11.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21145000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21145000"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Danilo Ritz, Maja Vuk, Philipp Kirchner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2301"}], "href": "https://doi.org/10.1038/ncb2301"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21822278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21822278"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Klara Acs, Martijn S Luijsterburg, Leena Ackermann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2188"}], "href": "https://doi.org/10.1038/nsmb.2188"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22120668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22120668"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Hajime Niwa, Caroline A Ewens, Chun Tsang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of the N-domain in the ATPase activity of the mammalian AAA ATPase p97/VCP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.302778"}], "href": "https://doi.org/10.1074/jbc.M111.302778"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22270372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22270372"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Stefan Kernstock, Erna Davydova, Magnus Jakobsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysine methylation of VCP by a member of a novel human protein methyltransferase family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms2041"}], "href": "https://doi.org/10.1038/ncomms2041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22948820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22948820"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Emily J Davis, Christophe Lachaud, Paul Appleton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2394"}], "href": "https://doi.org/10.1038/nsmb.2394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23042607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23042607"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "James A Olzmann, Caleb M Richter, Ron R Kopito "}, {"type": "b", "children": [{"type": "t", "text": "Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1213738110"}], "href": "https://doi.org/10.1073/pnas.1213738110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23297223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23297223"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Michael A Gonzalez, Shawna M Feely, Fiorella Speziani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awu224"}], "href": "https://doi.org/10.1093/brain/awu224"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25125609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25125609"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Alexander Buchberger, Hermann Schindelin, Petra Hänzelmann "}, {"type": "b", "children": [{"type": "t", "text": "Control of p97 function by cofactor binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2015.08.028"}], "href": "https://doi.org/10.1016/j.febslet.2015.08.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26320413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26320413"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Emily E Blythe, Kristine C Olson, Vincent Chau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP•NPLOC4•UFD1L is enhanced by a mutation that causes multisystem proteinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1706205114"}], "href": "https://doi.org/10.1073/pnas.1706205114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28512218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28512218"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Claire E Hall, Zhi Yao, Minee Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2017.05.024"}], "href": "https://doi.org/10.1016/j.celrep.2017.05.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28564594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28564594"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Lasse Stach, Paul S Freemont "}, {"type": "b", "children": [{"type": "t", "text": "The AAA+ ATPase p97, a cellular multitool."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20160783"}], "href": "https://doi.org/10.1042/BCJ20160783"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28819009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28819009"}]}]}]}