NVL

Last update 08 May 2025

Basic Info

Synonyms

Nuclear valosin-containing protein-like, nuclear VCP like, Nuclear VCP-like protein

+ [3]

Introduction

Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT (PubMed:22226966). Involved in both early and late stages of the pre-rRNA processing pathways (PubMed:26166824). Spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus (PubMed:15469983, PubMed:16782053, PubMed:26456651, PubMed:29107693). Catalyzes the release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles through the ATPase activity (PubMed:26456651, PubMed:28416111, PubMed:29107693).

100 Clinical Results associated with NVL

100 Translational Medicine associated with NVL

0 Patents (Medical) associated with NVL

Literatures (Medical) associated with NVL

01 Jan 2025·Biochemical and Biophysical Research Communications

Pre-ribosomal WDR74 module coordinates the early and late pre-rRNA processing stages for the NVL2-mediated regulation of 60S ribosome biogenesis

Article

Author: Izumikawa, Keiichi ; Nobe, Yuko ; Ohga, Takayuki ; Taoka, Masato ; Miyao, Sotaro ; Nagahama, Masami ; Hirooka, Yuya

WD repeat domain 74 (WDR74) is a nucleolar protein involved in the early stages of pre-60S maturation in the ribosome biogenesis pathway. In later stages, WDR74 interacts with MTR4, an RNA helicase that functions with the exosome nuclease complex, and is dissociated upon ATP hydrolysis by the chaperone-like nuclear VCP-like 2 (NVL2) AAA-ATPase. We previously reported that ATP hydrolysis-defective NVL2 causes aberrant accumulation of WDR74 on the MTR4-exosome complex at the nucleolar periphery and in the nucleoplasm and that this nuclear redistribution of WDR74 leads to the unusual cleavage of the early rRNA precursor within the internal transcribed spacer 1 sequence. However, the precise mechanisms underlying this NVL2-mediated regulation is largely obscure. In this study, co-immunoprecipitation combined with mass spectrometry revealed that WDR74 functions as part of a pre-ribosomal subcomplex, termed the WDR74 module, consisting of eukaryotic conserved WDR74, RPF1, MAK16, and RRP1. Each component of the WDR74 module was mutually essential for the interaction of other members with MTR4, and all components were required for the accurate cleavage of pre-rRNA during 60S ribosome biogenesis. Moreover, impaired release of WDR74 from the MTR4-exosome complex caused by NVL2 dysfunction prevented MTR4 from recruiting PICT1, an MTR4 adaptor protein required for the 3'-end maturation of 5.8S rRNA. Our results highlight the key role of the WDR74 module in coordinating the early pre-rRNA cleavage and late processing of pre-5.8S rRNAs.

31 Dec 2024·Hematology

Hub genes and associated drugs for multiple myeloma with 1q21+: identified by bioinformatic analysis

Article

Author: Xu, Zhiqiang ; Chen, Yamei ; Yu, Jieni

While 1q21+ was common genetic alteration and found to have adverse effect on prognosis, the underlying genes remain unclear. Identification of related genes may provide additional help for rational intervention. The microarray dataset GSE2658 associated with MM was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were obtained, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate their functions. The hub genes were derived from the combined results of up-regulated DEGs and weighted gene coexpression network analysis (WGCNA). The receiver operating characteristic (ROC) curves of hub genes were plotted to evaluate correlation with 1q21+. Survival analysis and drug-gene interaction of hub genes were performed separately to find the prognostic value and potential targeted drugs. A total of 55 DEGs were identified. GO and KEGG pathway analyses suggested that the DEGs were related to several pathways of cell proliferation. NVL, IL6R, DUSP23 were proven to be highly correlated with 1q21+ and have adverse effects on prognosis. IL6R, DUSP23 were matched to known interaction-drug. This study revealed potential roles of hub genes in the pathogenesis and progression of MM with 1q21+, further investigations are needed to elucidate the mechanisms.

01 Oct 2024·Rheumatology

Autoantibodies to nuclear valosin-containing protein-like protein: systemic sclerosis-specific antibodies revealed by in vitro human proteome

Article

Author: Yamaguchi, Kei ; Matsuda, Kazuki M ; Fujio, Keishi ; Norimatsu, Yuta ; Shoda, Hirofumi ; Sato, Ayaka ; Okumura, Taishi ; Goshima, Naoki ; Matsushita, Takashi ; Yumi, Murakami ; Sato, Shinichi ; Ogawa, Koji ; Yoshizaki-Ogawa, Asako ; Matsunaka, Hiroshi ; Hisamoto, Teruyoshi ; Ono, Chihiro ; Kono, Masanori ; Kuzumi, Ai ; Okamura, Tomohisa ; Kotani, Hirohito ; Kawanabe, Ruriko ; Yoshizaki, Ayumi ; Fukasawa, Takemichi ; Miya, Ayako ; Uchino, Rikako

AbstractObjectivesTo identify and characterize undescribed systemic sclerosis (SSc)-specific autoantibodies targeting nucleolar antigens and to assess their clinical significance.MethodsWe conducted proteome-wide autoantibody screening (PWAS) against serum samples from SSc patients with nucleolar patterned anti-nuclear antibodies (NUC-ANAs) of specific antibodies (Abs) unknown, utilizing wet protein arrays fabricated from in vitro human proteome. Controls included SSc patients with already-known SSc-specific autoantibodies, patients with other connective tissue diseases and healthy subjects. The selection of nucleolar antigens was performed by database search in the Human Protein Atlas. The presence of autoantibodies was certified by immunoblots and immunoprecipitations. Indirect immunofluorescence assays on HEp-2 cells were also conducted. Clinical assessment was conducted by retrospective review of electronic medical records.ResultsPWAS identified three candidate autoantibodies, including anti-nuclear valosin-containing protein-like (NVL) Ab. Additional measurements in disease controls revealed that only anti-NVL Abs are exclusively detected in SSc. Detection of anti-NVL Abs was reproduced by conventional assays such as immunoblotting and immunoprecipitation. Indirect immunofluorescence assays demonstrated homogeneous nucleolar patterns. Anti-NVL Ab-positive cases were characterized by significantly low prevalence of diffuse skin sclerosis and interstitial lung disease, compared with SSc cases with NUC-ANAs other than anti-NVL Abs, such as anti-U3-RNP and anti-Th/To Abs.ConclusionAnti-NVL Ab is an SSc-specific autoantibody associated with a unique combination of clinical features, including limited skin sclerosis and lack of lung involvement.

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NVL

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