ArticleJournal of hepatology2011
Nucleoplasmic calcium regulates cell proliferation through legumain.
Article in Journal of hepatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Clinicopathologic significance of legumain overexpression in cancer: a systematic review and meta-analysis.Scientific reports · 2015Pooled it
- Etoposide-induced cancer cell death: roles of mitochondrial VDAC1 and calpain, and resistance mechanisms.Molecular oncology · 2025Article
- Cleavage of tropomodulin-3 by asparagine endopeptidase promotes cancer malignancy by actin remodeling and SND1/RhoA signaling.Journal of experimental & clinical cancer research : CR · 2022Article
- Activation and Migration of Human Skeletal Muscle Stem Cells In Vitro Differently Rely on Calcium Signals.Cells · 2022Article
- Systematic analysis of the expression and prognostic value of ITPR1 and correlation with tumor infiltrating immune cells in breast cancer.BMC cancer · 2022Article
- Network analysis of hepatocellular carcinoma liquid biopsies augmented by single-cell sequencing data.Frontiers in genetics · 2022Article
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- The Mechanism of Asparagine Endopeptidase in the Progression of Malignant Tumors: A Review.Cells · 2021Review
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- The construction of the novel magnetic prodrug FeRSC advances · 2020Article
- Role of Asparagine Endopeptidase in Mediating Wild-Type p53 Inactivation of Glioblastoma.Journal of the National Cancer Institute · 2020Article
- δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities.Translational neurodegeneration · 2020Review
- Inositol 1,4,5-trisphosphate receptor in the liver: Expression and function.World journal of gastroenterology · 2019Review
- Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP.International journal of biological sciences · 2019Article
- Article
- Calcium Signaling in Liver Injury and Regeneration.Frontiers in medicine · 2018Review
- Delta-Secretase Phosphorylation by SRPK2 Enhances Its Enzymatic Activity, Provoking Pathogenesis in Alzheimer's Disease.Molecular cell · 2017Article
- The expression of asparaginyl endopeptidase promotes growth potential in epithelial ovarian cancer.Cancer biology & therapy · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsNucleoplasmic Ca(2+) regulates cell growth in the liver, but the proteins through which this occurs are unknown.
methodsWe used Rapid Subtraction Hybridization (RaSH) to subtract genes in SKHep1 liver cells expressing the Ca(2+) buffer protein parvalbumin (PV) targeted to the nucleus, from genes in cells expressing a mutated form of nuclear-targeted PV which has one of two Ca(2+)-binding sites inactivated. The subtraction permitted the selection of genes whose expression was affected by a small alteration in nuclear Ca(2+) concentration.
resultsThe asparaginyl endopeptidase legumain (LGMN) was identified in this screening. When Ca(2+) was buffered in the nucleus of SKHep1 cells, LGMN mRNA was decreased by 97%, in part by a transcriptional mechanism, and decreased expression at the protein level was observed by immunoblot and immunofluorescence. Treatment with hepatocyte growth factor increased LGMN expression. Knockdown of LGMN by siRNA decreased proliferation of SKHep1 cells by ∼50% as measured both by BrdU uptake and mitotic index, although an inhibitor of LGMN activity did not affect BrdU incorporation. A significant reduction in the fraction of cells in G2/M phase was seen as well. This was associated with increases in the expression of cyclins A and E. Furthermore, LGMN expression was increased in hepatocellular carcinoma cells relative to normal hepatocytes in the same specimens.
conclusionsThese findings suggest a new role for LGMN and provide evidence that nuclear Ca(2+) signals regulate cell proliferation in part through the modulation of LGMN expression. Increased expression of LGMN may be involved in liver carcinogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.