scholarly journals Heterogeneous nuclear ribonucleoprotein (hnRNP) L promotes DNA damage-induced cell apoptosis by enhancing the translation of p53

Oncotarget ◽  
2017 ◽  
Vol 8 (31) ◽  
pp. 51108-51122 ◽  
Author(s):  
Ji-Young Seo ◽  
Do-Yeon Kim ◽  
Seong-Hoon Kim ◽  
Hyo-Jin Kim ◽  
Hye Guk Ryu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Apoptosis ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein

scholarly journals A proteomics approach for the identification of nucleophosmin and heterogeneous nuclear ribonucleoprotein C1/C2 as chromatin-binding proteins in response to DNA double-strand breaks

2005 ◽  
Vol 388 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Seung Yun LEE ◽  
Ji-Hye PARK ◽  
Sungsu KIM ◽  
Eun-Jung PARK ◽  
Yungdae YUN ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Binding Proteins ◽  
Double Strand Breaks ◽  
Nuclear Proteins ◽  
Chromatin Binding ◽  
Strand Breaks ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Proteomics Approach ◽  
Nuclear Ribonucleoprotein

Double-strand breaks (DSBs) of chromosomal DNA trigger the cellular response that activates the pathways for DNA repair and cell-cycle checkpoints, and sometimes the pathways leading to cell death if the damage is too severe to be tolerated. Evidence indicates that, upon generation of DNA DSBs, many nuclear proteins that are involved in DNA repair and checkpoints are recruited to chromatin around the DNA lesions. In the present study we used a proteomics approach to identify DNA-damage-induced chromatin-binding proteins in a systematic way. Two-dimensional gel analysis for protein extracts of chromatin from DNA-damage-induced and control HeLa cells identified four proteins as the candidates for DNA-damage-induced chromatin-binding proteins. MALDI–TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS analysis identified these proteins to be NPM (nucleophosmin), hnRNP (heterogeneous nuclear ribonucleoprotein) C1, hnRNP C2 and 37-kDa laminin-receptor precursor, and the identity of these proteins was further confirmed by immunoblot analysis with specific antibodies. We then demonstrated with chromatin-binding assays that NPM and hnRNP C1/C2, the abundant nuclear proteins with pleiotropic functions, indeed bind to chromatin in a DNA-damage-dependent manner, implicating these proteins in DNA repair and/or damage response. Immunofluorescence experiments showed that NPM, normally present in the nucleoli, is mobilized into the nucleoplasm after DNA damage, and that neither NPM nor hnRNP C1/C2 is actively recruited to the sites of DNA breaks. These results suggest that NPM and hnRNP C1/C2 may function at the levels of the global context of chromatin, rather than by specifically targeting the broken DNA.

scholarly journals Heterogeneous nuclear ribonucleoprotein E1 binds polycytosine DNA and monitors genome integrity

2021 ◽  
Vol 4 (9) ◽  
pp. e202000995
Author(s):  
Bidyut K Mohanty ◽  
Joseph AQ Karam ◽  
Breege V Howley ◽  
Annamarie C Dalton ◽  
Simon Grelet ◽  
...  
Keyword(s):  
Dna Damage ◽  
Binding Sites ◽  
Protein Translation ◽  
Genome Integrity ◽  
Nuclear Antigen ◽  
Dna Integrity ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Hydroxyurea Treatment ◽  
Nuclear Ribonucleoprotein ◽  
Hnrnp E1

Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) is a tumor suppressor protein that binds site- and structure-specifically to RNA sequences to regulate mRNA stability, facilitate alternative splicing, and suppress protein translation on several metastasis-associated mRNAs. Here, we show that hnRNP E1 binds polycytosine-rich DNA tracts present throughout the genome, including those at promoters of several oncogenes and telomeres and monitors genome integrity. It binds DNA in a site- and structure-specific manner. hnRNP E1-knockdown cells displayed increased DNA damage signals including γ-H2AX at its binding sites and also showed increased mutations. UV and hydroxyurea treatment of hnRNP E1-knockdown cells exacerbated the basal DNA damage signals with increased cell cycle arrest, activation of checkpoint proteins, and monoubiquitination of proliferating cell nuclear antigen despite no changes in deubiquitinating enzymes. DNA damage caused by genotoxin treatment localized to hnRNP E1 binding sites. Our work suggests that hnRNP E1 facilitates functions of DNA integrity proteins at polycytosine tracts and monitors DNA integrity at these sites.

scholarly journals DNA Damage-induced Heterogeneous Nuclear Ribonucleoprotein K SUMOylation Regulates p53 Transcriptional Activation

2012 ◽  
Vol 287 (36) ◽  
pp. 30789-30799 ◽  
Author(s):  
Federico Pelisch ◽  
Berta Pozzi ◽  
Guillermo Risso ◽  
Manuel Javier Muñoz ◽  
Anabella Srebrow
Keyword(s):  
Dna Damage ◽  
Transcriptional Activation ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein

scholarly journals Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation

2014 ◽  
Vol 42 (15) ◽  
pp. 9908-9924 ◽  
Author(s):  
Jen-Hao Yang ◽  
Yi-Ying Chiou ◽  
Shu-Ling Fu ◽  
I-Yun Shih ◽  
Tsai-Hsuan Weng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Rna Processing ◽  
Tumor Development ◽  
Arginine Methylation ◽  
Wild Type ◽  
Post Translational Modifications ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Damage Response ◽  
Nuclear Ribonucleoprotein

Abstract Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA-binding protein involved in chromatin remodeling, RNA processing and the DNA damage response. In addition, increased hnRNPK expression has been associated with tumor development and progression. A variety of post-translational modifications of hnRNPK have been identified and shown to regulate hnRNPK function, including phosphorylation, ubiquitination, sumoylation and methylation. However, the functional significance of hnRNPK arginine methylation remains unclear. In the present study, we demonstrated that the methylation of two essential arginines, Arg296 and Arg299, on hnRNPK inhibited a nearby Ser302 phosphorylation that was mediated through the pro-apoptotic kinase PKCδ. Notably, the engineered U2OS cells carrying an Arg296/Arg299 methylation-defective hnRNPK mutant exhibited increased apoptosis upon DNA damage. While such elevated apoptosis can be diminished through addition with wild-type hnRNPK, we further demonstrated that this increased apoptosis occurred through both intrinsic and extrinsic pathways and was p53 independent, at least in part. Here, we provide the first evidence that the arginine methylation of hnRNPK negatively regulates cell apoptosis through PKCδ-mediated signaling during DNA damage, which is essential for the anti-apoptotic role of hnRNPK in apoptosis and the evasion of apoptosis in cancer cells.

microR-505/heterogeneous nuclear ribonucleoprotein M inhibits hepatocellular carcinoma cell proliferation and induces cell apoptosis through the Wnt/β-catenin signaling pathway

2020 ◽  
Vol 14 (11) ◽  
pp. 981-996
Author(s):  
Xiaobin Chi ◽  
Yi Jiang ◽  
Yongbiao Chen ◽  
Lizhi Lv ◽  
Jianwei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Apoptosis Assay ◽  
Proliferation And Metastasis ◽  
Novel Strategy ◽  
Nuclear Ribonucleoprotein

Aim: This study aimed to investigate the expression of microRNA-505 (miR-505) and explore its clinical significance, biological function and mechanisms in hepatocellular carcinoma (HCC). Methods: Expression of miR-505 was measured in 128 paired HCC tissues and five cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay, Transwell migration, invasion assays and apoptosis assay were performed to explore the functional role of miR-505. The target gene of miR-505 was assessed using the bioinformatics assay and the related signaling pathway was confirmed using western blot. Results: Expression of miR-505 in HCC serum and tissues were downregulated. The overexpression of miR-505 in HCC cells inhibited cell proliferation and metastasis, as well as enhanced cell apoptosis by directly downregulating heterogeneous nuclear ribonucleoprotein M ( HNRNPM). The activity of the Wnt/β-catenin signaling pathway was suppressed by the overexpression of miR-505 but was promoted by the upregulation of HNRNPM. Conclusion: The results suggest that the regulation of miR-505/ HNRNPM may be a novel strategy to improve the targeted therapy of HCC.

scholarly journals ATM-dependent phosphorylation of heterogeneous nuclear ribonucleoprotein K promotes p53 transcriptional activation in response to DNA damage

Cell Cycle ◽  
2013 ◽  
Vol 12 (4) ◽  
pp. 698-704 ◽  
Author(s):  
Abdeladim Moumen ◽  
Christine Magill ◽  
Katherine Dry ◽  
Stephen P. Jackson
Keyword(s):  
Dna Damage ◽  
Transcriptional Activation ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein

Loss of heterogeneous nuclear ribonucleoprotein L (HNRNP L) leads to mitochondrial dysfunction, DNA damage response and caspase-dependent cell death in hematopoietic stem cells

2016 ◽  
Vol 44 (9) ◽  
pp. S78-S79 ◽  
Author(s):  
Anne Helness ◽  
Marie-Claude Gaudreau ◽  
Damien Grapton ◽  
Charles Vadnais ◽  
Jennifer Fraszczak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Dna Damage Response ◽  
Hematopoietic Stem ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Damage Response ◽  
Dependent Cell ◽  
Nuclear Ribonucleoprotein
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