ArticleThe Journal of biological chemistry2012
All human granzymes target hnRNP K that is essential for tumor cell viability.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Efficacy and immunological correlates of an mRNA-LNP vaccine for protection against an emerging rickettsial pathogen.Emerging microbes & infections · 2026Article
- Exploring GZMK as a prognostic marker and predictor of immunotherapy response in breast cancer: unveiling novel insights into treatment outcomes.Journal of cancer research and clinical oncology · 2024Article
- Heterogeneous nuclear ribonucleoprotein K promotes cap-independent translation initiation of retroviral mRNAs.Nucleic acids research · 2024Article
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
- hnRNP K induces HPV16 oncogene expression and promotes cervical cancerization.Journal of cancer research and clinical oncology · 2023Article
- Noncytotoxic functions of killer cell granzymes in viral infections.PLoS pathogens · 2021Review
- Intracellular and Extracellular Roles of Granzyme K.Frontiers in immunology · 2021Review
- Transcriptomic Profiles in Children With Septic Shock With or Without Immunoparalysis.Frontiers in immunology · 2021Article
- Type 1 diabetes cadaveric human pancreata exhibit a unique exocrine tissue proteomic profile.Proteomics · 2016Article
- Methylthioadenosine (MTA) Regulates Liver Cells Proteome and Methylproteome: Implications in Liver Biology and Disease.Molecular & cellular proteomics : MCP · 2016Article
- Reduced serpinB9-mediated caspase-1 inhibition can contribute to autoinflammatory disease.Oncotarget · 2016Article
- hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies.Cancer cell · 2015Article
- Perforin and granzymes: function, dysfunction and human pathology.Nature reviews. Immunology · 2015Review
- Proteomic-based approach to gain insight into reprogramming of THP-1 cells exposed to Leishmania donovani over an early temporal window.Infection and immunity · 2015Article
- Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation.Nucleic acids research · 2014Article
- Granzyme M: behind enemy lines.Cell death and differentiation · 2014Review
- Granzyme M targets topoisomerase II alpha to trigger cell cycle arrest and caspase-dependent apoptosis.Cell death and differentiation · 2014Article
- Heterogeneous nuclear ribonucleoprotein K supports vesicular stomatitis virus replication by regulating cell survival and cellular gene expression.Journal of virology · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Granule exocytosis by cytotoxic lymphocytes is the key mechanism to eliminate virus-infected cells and tumor cells. These lytic granules contain the pore-forming protein perforin and a set of five serine proteases called granzymes. All human granzymes display distinct substrate specificities and induce cell death by cleaving critical intracellular death substrates. In the present study, we show that all human granzymes directly cleaved the DNA/RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K), designating hnRNP K as the first known pan-granzyme substrate. Cleavage of hnRNP K was more efficient in the presence of RNA and occurred in two apparent proteolysis-sensitive amino acid regions, thereby dissecting the functional DNA/RNA-binding hnRNP K domains. HnRNP K was cleaved under physiological conditions when purified granzymes were delivered into living tumor cells and during lymphokine-activated killer cell-mediated attack. HnRNP K is essential for tumor cell viability, since knockdown of hnRNP K resulted in spontaneous tumor cell apoptosis with caspase activation and reactive oxygen species production. This apoptosis was more pronounced at low tumor cell density where hnRNP K knockdown also triggered a caspase-independent apoptotic pathway. This suggests that hnRNP K promotes tumor cell survival in the absence of cell-cell contact. Silencing of hnRNP K protein expression rendered tumor cells more susceptible to cellular cytotoxicity. We conclude that hnRNP K is indispensable for tumor cell viability and our data suggest that targeting of hnRNP K by granzymes contributes to or reinforces the cell death mechanisms by which cytotoxic lymphocytes eliminate tumor cells.
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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.