HSCARG, a novel regulator of H2A ubiquitination by downregulating PRC1 ubiquitin E3 ligase activity, is essential for cell proliferation

Li, Shangze; Zhang, Xiaodong; Zheng, Xiaofeng

doi:10.1093/nar/gku230

Cited by 25 publications

(17 citation statements)

References 52 publications

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“…IR treatment was performed following procedures described previously (30). After irradiation at 10 Gy, cells were incubated at 37 C for indicated time.…”

Section: Ir Treatmentmentioning

confidence: 99%

“…HeLa cells were transfected with the indicated plasmids using PEI and treated with 10 Gy IR. At 24 hours after transfection, cells were collected and fixed in precooled methanol for 8 minutes at À20 C following a procedure described previously (30). Images were obtained using a confocal microscope (Zeiss LSM-710 NLO and DuoScan) using a 40 Â or 63 Â oil objective lens.…”

Section: Immunofluorescence Microscopymentioning

confidence: 99%

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A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy

et al. 2018

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A competent DNA damage response (DDR) helps prevent cancer, but once cancer has arisen, DDR can blunt the efficacy of chemotherapy and radiotherapy that cause lethal DNA breakage in cancer cells. Thus, blocking DDR may improve the efficacy of these modalities. Here, we report a new DDR mechanism that interfaces with inflammatory signaling and might be blocked to improve anticancer outcomes. Specifically, we report that the ubiquitin-editing enzyme A20/TNFAIP3 binds and inhibits the E3 ubiquitin ligase RNF168, which is responsible for regulating histone H2A turnover critical for proper DNA repair. A20 induced after DNA damage disrupted RNF168-H2A interaction in a manner independent of its enzymatic activity. Furthermore, it inhibited accumulation of RNF168 and downstream repair protein 53BP1 during DNA repair. A20 was also required for disassembly of RNF168 and 53BP1 from damage sites after repair. Conversely, A20 deletion increased the efficiency of error-prone nonhomologous DNA end-joining and decreased error-free DNA homologous recombination, destablizing the genome and increasing sensitivity to DNA damage. In clinical specimens of invasive breast carcinoma, A20 was widely overexpressed, consistent with its candidacy as a therapeutic target. Taken together, our findings suggest that A20 is critical for proper functioning of the DDR in cancer cells and it establishes a new link between this NFκB-regulated ubiquitin-editing enzyme and the DDR pathway. This study identifies the ubiquitin-editing enzyme A20 as a key factor in mediating cancer cell resistance to DNA-damaging therapy, with implications for blocking its function to leverage the efficacy of chemotherapy and radiotherapy. .

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“…IR treatment was performed following procedures described previously (30). After irradiation at 10 Gy, cells were incubated at 37 C for indicated time.…”

Section: Ir Treatmentmentioning

confidence: 99%

Section: Immunofluorescence Microscopymentioning

confidence: 99%

A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy

et al. 2018

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“…To detect the effect of NLK on ATF5 ubiquitination, denaturing immunoprecipitation and ubiquitination analysis were performed as previously described (35). HEK293T cells were transfected with the indicated plasmids, and at 36 h posttransfection, the cells were washed with PBS and lysed with 1 volume of SDS lysis buffer (10% SDS in PBS).…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

Stabilization of ATF5 by TAK1–Nemo-Like Kinase Critically Regulates the Interleukin-1β-Stimulated C/EBP Signaling Pathway

Zhang

et al. 2015

Molecular and Cellular Biology

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“…C), but pronounced expression levels, of transporter genes associated with biocontrol at early time points is indicative of important functional roles early in antagonistic interactions with Sclerotinia . Other genes in this co‐expressed cluster included an oxidoreductase, a methyltransferase, two short‐chain dehydrogenase genes, a glycoside hydrolase, an HSCARG dehydrogenase [involved in NADPH sensing (Zhao et al ., ) and regulation of H2A ubiquitination (Hu et al ., )] or chaperone proteins, all implicated in the modification of metabolites or gene regulation. The fact that 16 of the 18 genes in the MSM early response cluster have predicted functions (enzymatic and transport) implies that modification of small molecules/biosynthetic enzymes is a key early event in the establishment of GD12 biocontrol capability.…”

Section: Resultsmentioning

confidence: 82%

Transcriptional reprogramming underpins enhanced plant growth promotion by the biocontrol fungus Trichoderma hamatum GD12 during antagonistic interactions with Sclerotinia sclerotiorum in soil

Shaw

Cocq

Paszkiewicz

et al. 2016

Molecular Plant Pathology

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SUMMARYThe free-living soil fungus Trichoderma hamatum strain GD12 is notable amongst Trichoderma strains in both controlling plant diseases and stimulating plant growth, a property enhanced during its antagonistic interactions with pathogens in soil. These attributes, alongside its markedly expanded genome and proteome compared with other biocontrol and plant growth-promoting Trichoderma strains, imply a rich potential for sustainable alternatives to synthetic pesticides and fertilizers for the control of plant disease and for increasing yields. The purpose of this study was to investigate the transcriptional responses of GD12 underpinning its biocontrol and plant growth promotion capabilities during antagonistic interactions with the pathogen Sclerotinia sclerotiorum in soil. Using an extensive mRNA-seq study capturing different time points during the pathogen-antagonist interaction in soil, we show that dynamic and biphasic signatures in the GD12 transcriptome underpin its biocontrol and plant (lettuce) growth-promoting activities. Functional predictions of differentially expressed genes demonstrate the enrichment of transcripts encoding proteins involved in transportation and oxidation-reduction reactions during both processes and an over-representation of siderophores. We identify a biphasic response during biocontrol characterized by a significant induction of transcripts encoding small-secreted cysteine-rich proteins, secondary metabolite-producing gene clusters and genes unique to GD12. These data support the hypothesis that Sclerotinia biocontrol is mediated by the synthesis and secretion of antifungal compounds and that GD12's unique reservoir of uncharacterized genes is actively recruited during the effective biological control of a plurivorous plant pathogen.

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HSCARG, a novel regulator of H2A ubiquitination by downregulating PRC1 ubiquitin E3 ligase activity, is essential for cell proliferation

Cited by 25 publications

References 52 publications

A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy

A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy

Stabilization of ATF5 by TAK1–Nemo-Like Kinase Critically Regulates the Interleukin-1β-Stimulated C/EBP Signaling Pathway

Transcriptional reprogramming underpins enhanced plant growth promotion by the biocontrol fungus Trichoderma hamatum GD12 during antagonistic interactions with Sclerotinia sclerotiorum in soil

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