Y14 governs p53 expression and modulates DNA damage sensitivity

Lu, Cuihua; Lee, Chi‐Chieh; Tseng, Ching-Tzu; Tarn, Woan‐Yuh

doi:10.1038/srep45558

Cited by 23 publications

(45 citation statements)

References 26 publications

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“…Therefore we examined the expression of a panel of DDR signaling factors in Y14-depleted HeLa cells. Immunoblotting showed that Y14 depletion induced p53β and γH2AX, as previously reported (Lu et al., 2017) and reduced the level of three major upstream DDR kinases, namely, ATM, ATR, and DNA-PK (Figure 2C). A similar result was obtained in Y14-depleted MCF7 and U2OS cells (Figure S4A).…”

Section: Resultssupporting

confidence: 87%

The RNA Processing Factor Y14 Participates in DNA Damage Response and Repair

Chuang

et al. 2019

iScience

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SummaryDNA repair deficiency leads to genome instability and hence human disease. Depletion of the RNA processing factor Y14/RBM8A in cultured cells or Rbm8a haplodeficiency in the developing mouse cortex results in the accumulation of DNA damage. Y14 depletion differentially affected the expression of DNA damage response (DDR) factors and induced R-loops, both of which threaten genomic stability. Immunoprecipitation coupled with mass spectrometry revealed DDR factors as potential Y14-interacting partners. Further results confirmed that Y14 interacts with Ku and several DDR factors in an ATM-dependent manner. Y14 co-fractionated with Ku in chromatin-enriched fractions and further accumulated on chromatin upon DNA damage. Y14 knockdown delayed recruitment of DDR factors to DNA damage sites and formation of γH2AX foci and also led to Ku retention on chromatin. Accordingly, Y14 depletion compromised the efficiency of DNA end joining. Therefore Y14 likely plays a direct role in DNA damage repair via its interaction with DDR factors.

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Section: Resultssupporting

confidence: 87%

The RNA Processing Factor Y14 Participates in DNA Damage Response and Repair

Chuang

et al. 2019

iScience

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“…In contrast to these unique expression events, 12 proteins were significantly altered across all five RXFP3 expression levels (Supplementary Figure 3: PRR14L, SCYL1, CCDC9, NEK7, HIST1H3A, ATPIF1, CDCA2, PAGR1, POTEKP, MTMR1, ZCCHC3, MEPCE). Many of these commonly regulated proteins are known to be associated with energy balance regulation (PRR14L [40]), inflammaging (NEK7 [41]; ATPIF1 [42]), aging associated DNA damage (SCYL1 [43]; CCDC9 [44]; HIST1H3A [45]; ATPIF1 [46]; PAGR1 [47]; ZCCHC3 [48]) or cell senescence (CDCA2 [49]). As such it appears that in addition to expression level effects, a core functionality of the RXFP3 was also evident, which was tightly linked to age-related pathologies.…”

Section: Resultsmentioning

confidence: 99%

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Gastel

Leysen

Santos‐Otte

et al. 2019

Aging

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DNA damage response (DDR) processes, often caused by oxidative stress, are important in aging and -related disorders. We recently showed that G protein-coupled receptor (GPCR) kinase interacting protein 2 (GIT2) plays a key role in both DNA damage and oxidative stress. Multiple tissue analyses in GIT2KO mice demonstrated that GIT2 expression affects the GPCR relaxin family peptide 3 receptor (RXFP3), and is thus a therapeutically-targetable system. RXFP3 and GIT2 play similar roles in metabolic aging processes. Gaining a detailed understanding of the RXFP3-GIT2 functional relationship could aid the development of novel anti-aging therapies. We determined the connection between RXFP3 and GIT2 by investigating the role of RXFP3 in oxidative stress and DDR. Analyzing the effects of oxidizing (H2O2) and DNA-damaging (camptothecin) stressors on the interacting partners of RXFP3 using Affinity Purification-Mass Spectrometry, we found multiple proteins linked to DDR and cell cycle control. RXFP3 expression increased in response to DNA damage, overexpression, and Relaxin 3-mediated stimulation of RXFP3 reduced phosphorylation of DNA damage marker H2AX, and repair protein BRCA1, moderating DNA damage. Our data suggests an RXFP3-GIT2 system that could regulate cellular degradation after DNA damage, and could be a novel mechanism for mitigating the rate of age-related damage accumulation.

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“…It is also known to be the core protein of nonsense-mediated mRNA decay (NMD), which monitors abnormal mRNA in eukaryotes [8, 9]. RBM8A is related to RNA transcription, translation, cell cycle regulation and apoptosis regulation [10, 11], and it is also involved in several crucial cell signaling pathways [12–15], in which it plays an important role in tumorigenesis and development. Abnormal expression of RBM8A was first detected in cervical cancer [7], and its overexpression was subsequently detected in various malignant tumors, including non-small cell lung cancer and myeloma [16–18].…”

Section: Introductionmentioning

confidence: 99%

Expression and gene regulation network of RBM8A in hepatocellular carcinoma based on data mining

Lin

Liang

Qiu

et al. 2019

Aging

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RNA binding motif protein 8A (RBM8A) is an RNA binding protein in a core component of the exon junction complex. Abnormal RBM8A expression is associated with carcinogenesis. We used sequencing data from the Cancer Genome Atlas database and Gene Expression Omnibus, analyzed RBM8A expression and gene regulation networks in hepatocellular carcinoma (HCC). Expression was analyzed using OncomineTM and Gene Expression Profiling Interactive Analysis tools, while RBM8A alterations and related functional networks were identified using cBioPortal. LinkedOmics was used to identify differential gene expression with RBM8A and to analyze Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Gene enrichment analysis examined target networks of kinases, miRNAs and transcription factors. We found that RBM8A is overexpressed and the RBM8A gene often amplified in HCC. Expression of this gene is linked to functional networks involving the ribosome and RNA metabolic signaling pathways. Functional network analysis suggested that RBM8A regulates the spliceosome, ribosome, DNA replication and cell cycle signaling via pathways involving several cancer-related kinases, miRNAs and E2F Transcription Factor 1. Our results demonstrate that data mining efficiently reveals information about RBM8A expression and potential regulatory networks in HCC, laying a foundation for further study of the role of RBM8A in carcinogenesis.

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Y14 governs p53 expression and modulates DNA damage sensitivity

Cited by 23 publications

References 26 publications

The RNA Processing Factor Y14 Participates in DNA Damage Response and Repair

The RNA Processing Factor Y14 Participates in DNA Damage Response and Repair

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Expression and gene regulation network of RBM8A in hepatocellular carcinoma based on data mining

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