A Novel Transcription Complex That Selectively Modulates Apoptosis of Breast Cancer Cells through Regulation of FASTKD2

Yeung, Kay T.; Das, Sharmistha; Zhang, Jin; Lomniczi, Alejandro; Ojeda, Sergio R.; Xu, Chong; Neubert, Thomas A.; Samuels, Herbert H.

doi:10.1128/mcb.01381-10

Cited by 57 publications

(98 citation statements)

References 41 publications

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“…A mutation in the FASTKD2 gene was reported to cause an isolated complex IV deficiency in a patient presenting with mitochondrial encephalomyopathy, but the molecular mechanism for this defect was not investigated (Ghezzi et al, 2008). A role for FASTKD2 in apoptosis of both breast and non-breast cancer cells has also been suggested; however, the apoptotic response was independent of its mitochondrial localization (Yeung et al, 2011). Thus, the precise roles of DHX30 and FASTKD2 in mitochondria remain to be determined.…”

Section: Characterization Of the Rna Granule Proteomementioning

confidence: 96%

Mitochondrial RNA Granules Are Centers for Posttranscriptional RNA Processing and Ribosome Biogenesis

Antonická¹,

Shoubridge²

2015

Cell Reports

250

282

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Cytoplasmic RNA granules play a central role in mRNA metabolism, but the importance of mitochondrial RNA granules remains relatively unexplored. We characterized their proteome and found that they contain a large toolbox of proteins dedicated to RNA metabolism. Investigation of four uncharacterized putative RNA-binding proteins-two RNA helicases, DHX30 and DDX28, and two proteins of the Fas-activated serine-threonine kinase (FASTKD) family, FASTKD2 and FASTKD5-demonstrated that both helicases and FASTKD2 are required for mitochondrial ribosome biogenesis. RNA-sequencing (RNA-seq) analysis showed that DDX28 and FASTKD2 bound the 16S rRNA. FASTKD5 is required for maturing precursor mRNAs that are not flanked by tRNAs and that therefore cannot be processed by the canonical mRNA maturation pathway. Silencing FASTKD5 rendered mature COX I mRNA almost undetectable, which severely reduced the synthesis of COX I, resulting in a complex IV assembly defect. These data demonstrate that mitochondrial RNA granules are centers for posttranscriptional RNA processing and the biogenesis of mitochondrial ribosomes.

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Section: Characterization Of the Rna Granule Proteomementioning

confidence: 96%

Mitochondrial RNA Granules Are Centers for Posttranscriptional RNA Processing and Ribosome Biogenesis

Antonická¹,

Shoubridge²

2015

Cell Reports

250

282

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“…Although the majority of works available in the literature proposes a role for IRF2BP2 as a repressor in the regulation of diverse genes [4][5][6][7][8][9], there is some evidence that IRF2BP2 may also act as a positive regulator of gene expression [10,11]. The mechanisms by which IRF2BP2 mediates its repression or induction in the course of gene-expression regulation have not been established and may involve interaction with the DNA and/or with different proteins that vary according to the context.…”

Section: Introductionmentioning

confidence: 95%

“…Originally, IRF2BP proteins were identified as nuclear transcriptional corepressors that were dependent on IRF2; binding to IRF2 results in their recruitment to the DNA, where they can mediate their repressor function [4]. More recently, IRF2BP2 was identified as a transcriptional repressor in several other biologic contexts that did not necessarily require IRF2 participation [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 97%

IRF2BP2 transcriptional repressor restrains naive CD4 T cell activation and clonal expansion induced by TCR triggering

Sécca

Faget

Hanschke

et al. 2016

Journal of Leukocyte Biology

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CD4 T cell activation and differentiation mechanisms constitute a complex and intricate signaling network involving several regulatory proteins. IRF2BP2 is a transcriptional repressor that is involved in gene-expression regulation in very diverse biologic contexts. Information regarding the IRF2BP2 regulatory function in CD4 T lymphocytes is very limited and suggests a role for this protein in repressing the expression of different cytokine genes. Here, we showed that Irf2bp2 gene expression was decreased in CD4 T cells upon activation. To investigate the possible regulatory roles for IRF2BP2 in CD4 T cell functions, this protein was ectopically expressed in murine primary-activated CD4 T lymphocytes through retroviral transduction. Interestingly, ectopic expression of IRF2BP2 led to a reduction in CD25 expression and STAT5 phosphorylation, along with an impaired proliferative capacity. The CD69 expression was also diminished in IRF2BP2-overexpressing cells, whereas CD44 and CD62L levels were not altered. In vivo, transferred, IRF2BP2-overexpressing, transduced cells displayed an impaired expansion capacity compared with controls. Furthermore, overexpression of IRF2BP2 in differentiated Th cells resulted in slightly reduced IL-4 and pro-TGF-β production in Th2 and iT but had no effect on IFN-γ or IL-17 expression in Th1 and Th17 cells, respectively. Taken together, our data suggest a role for IRF2BP2 in regulating CD4 T cell activation by repressing proliferation and the expression of CD25 and CD69 induced by TCR stimuli.

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“…Many of the interactions, however, are highly specific to one or a few C2H2-ZF proteins. The established interaction of YY1 with the INO80 complex (Cai et al 2007) is exclusive among the 118 proteins examined, while components of the repressive DIF-1 complex (Yeung et al 2011) interact specifically with KLF10, and Groucho-related proteins TLE1, TLE3, and AES all interact only with OSR2 (Fig. 5A).…”

Section: C2h2-zf Proteins Often Have Unique Ppi Profilesmentioning

confidence: 99%

Multiparameter functional diversity of human C2H2 zinc finger proteins

et al. 2016

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C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether or how these proteins regulate transcription. Most of the ∼700 human C2H2-ZF proteins also contain at least one KRAB, SCAN, BTB, or SET domain, suggesting that they may have common interacting partners and/or effector functions. Here, we report a multifaceted functional analysis of 131 human C2H2-ZF proteins, encompassing DNA binding sites, interacting proteins, and transcriptional response to genetic perturbation. We confirm the expected diversity in DNA binding motifs and genomic binding sites, and provide motif models for 78 previously uncharacterized C2H2-ZF proteins, most of which are unique. Surprisingly, the diversity in protein–protein interactions is nearly as high as diversity in DNA binding motifs: Most C2H2-ZF proteins interact with a unique spectrum of co-activators and co-repressors. Thus, multiparameter diversification likely underlies the evolutionary success of this large class of human proteins.

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A Novel Transcription Complex That Selectively Modulates Apoptosis of Breast Cancer Cells through Regulation of FASTKD2

Cited by 57 publications

References 41 publications

Mitochondrial RNA Granules Are Centers for Posttranscriptional RNA Processing and Ribosome Biogenesis

Mitochondrial RNA Granules Are Centers for Posttranscriptional RNA Processing and Ribosome Biogenesis

IRF2BP2 transcriptional repressor restrains naive CD4 T cell activation and clonal expansion induced by TCR triggering

Multiparameter functional diversity of human C2H2 zinc finger proteins

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