Gadd45β is a pro-survival factor associated with stress-resistant tumors

Engelmann, Afra; Speidel, Daniel; Bornkamm, Georg W.; Deppert, Wolfgang; Stocking, Carol

doi:10.1038/sj.onc.1210772

Cited by 34 publications

(27 citation statements)

References 39 publications

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“…In addition, it has been reported that Gadd45b mediates the protective effects of CD40 against Fas-induced apoptosis in B lymphocytes (26). Additional evidence for an antiapoptotic function of Gadd45b has been supported by the fact that Gadd45b protects myeloid hematopoietic cells and fibroblasts from apoptosis induced by genotoxic stress (27) and serum withdrawal (28), respectively. These results reflect the multiple functions of Gadd45 family proteins in regulating intracellular processes and suggest that the function of Gadd45 family proteins might be dependent on the proteins that interact with them.…”

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confidence: 69%

Gadd45b Mediates Fas-induced Apoptosis by Enhancing the Interaction between p38 and Retinoblastoma Tumor Suppressor

Cho

Park

Hwang

et al. 2010

Journal of Biological Chemistry

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Gadd45b has been known as a positive mediator of apoptosis induced by certain cytokines and oncogenes. Here, we identified Gadd45b as an effector of Fas-induced apoptosis and found that p38-mediated Rb hyperphosphorylation is one of the mechanisms of Fas-induced apoptosis in murine hepatocyte AML12 cells. Gadd45b has been shown to activate p38 through its physical interaction with MTK1 and induce apoptosis. However, in this study, we have showed that the function of Gadd45b during Fas-induced apoptosis in AML12 cells is different from that reported in previous studies. Depletion of Gadd45b expression did not inhibit the phosphorylation of p38, but it suppressed p38-mediated Rb phosphorylation and apoptosis in response to Fas stimulation by reducing the interaction between p38 and Rb. Ectopic expression of Gadd45b was sufficient to enhance this interaction. These findings suggest that Gadd45b mediates p38-induced Rb phosphorylation by enhancing the interaction between p38 and Rb during Fas-induced apoptosis in murine hepatocytes.

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confidence: 69%

Gadd45b Mediates Fas-induced Apoptosis by Enhancing the Interaction between p38 and Retinoblastoma Tumor Suppressor

Cho

Park

Hwang

et al. 2010

Journal of Biological Chemistry

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“…Loss of Sdc1, which appears to be negatively regulated by Stat3, correlates with higher malignancy of ductal breast cancer cells and with epithelial to mesenchimal transition of epithelial cancer cells (24). Gadd45b is a prosurvival factor associated to stress resistance in tumors and its overexpression can transform NIH 3T3 fibroblasts (25). Nfil3 mediates IL-3 prosurvival functions in pro-B cells and its activation by dexamethasone correlates with down-regulation of proinflammatory mediators that are also down-regulated in tumor cells with constitutively active Stat3 (26).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Vallania

Schiavone

Dewilde

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The identification of direct targets of transcription factors is a key problem in the study of gene regulatory networks. However, the use of high throughput experimental methods, such as ChIP-chip and ChIP-sequencing, is limited by their high cost and strong dependence on cellular type and context. We developed a computational method for the genome-wide identification of functional transcription factor binding sites based on positional weight matrices, comparative genomics, and gene expression profiling. The method was applied to Stat3, a transcription factor playing crucial roles in inflammation, immunity and oncogenesis, and able to induce distinct subsets of target genes in different cell types or conditions. A newly generated positional weight matrix enabled us to assign affinity scores of high specificity, as measured by EMSA competition assays. Phylogenetic conservation with 7 vertebrate species was used to select the binding sites most likely to be functional. Validation was carried out on predicted sites within genes identified as differentially expressed in the presence or absence of Stat3 by microarray analysis. Twelve of the fourteen sites tested were bound by Stat3 in vivo, as assessed by Chromatin Immunoprecipitation, allowing us to identify 9 Stat3 transcriptional targets. Given its high validation rate, and the availability of large transcription factor-dependent gene expression datasets obtained under diverse experimental conditions, our approach appears to be a valid alternative to high-throughput experimental assays for the discovery of novel direct targets of transcription factors.chromatin immunoprecipitation ͉ phylogenetic footprint ͉ positional weight matrix ͉ Stat3 binding sites ͉ Stat3 target genes F unctional transcription factor binding sites (TFBSs) can be identified on a genomic scale either by computational approaches or through elaborated procedures such as chromatin immunoprecipitation followed by either genomic microchip hybridization (ChIP on Chip) or deep sequencing (ChIP and Sequencing) (1). These have the advantage of directly measuring the in vivo occupancy of genomic sites. By definition however, each experiment will only be able to identify sites bound under the specific conditions analyzed, i.e., separate experiments will have to be performed for each condition/tissue type of interest, and this will be particularly true for the many transcription factors (TF) that are known to induce distinct sets of genes in different tissues. Indeed, sets of TFBSs identified with these techniques in different conditions often show limited overlap. The predictions based on computational sequence analysis (2), however, are in principle independent of the cellular context. The ample collection of candidate BSs thus produced will then be available to identify transcriptional targets either as such or within lists of differentially expressed genes generated by microarray experiments, in many cases already available through public databases.The standard way to describe degenerate cis-regulator...

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“…The genes NUDT9, TIMM44, SESN2, and GADD45B are localized in the mitochondria and respond to oxidative stress (64 -67). GADD45B is an activator of pro-survival p38 MAPK signaling (66,68,69). Both TIMM44 and NUDT9 localize to the mitochondria, and TIMM44 acts as a translocase to allow import of peptides/proteins to the inner mitochondrial membrane (70).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Endoplasmic Reticulum Stress Response Element Regulated by XBP1

Misiewicz

Déry

Foveau

et al. 2013

Journal of Biological Chemistry

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Background: Endoplasmic reticulum (ER) stress maintains cellular protein homeostasis. Results: A novel ER stress-responsive element, ERSE-26, identified in 38 genes, is regulated by sXBP1 during ER stress. Conclusion: ER stress increases levels of prion and other proteins not previously known to be involved in the ER stress response. Significance: ERSE-26 implicates novel genes regulated by the ER stress response.

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Gadd45β is a pro-survival factor associated with stress-resistant tumors

Cited by 34 publications

References 39 publications

Gadd45b Mediates Fas-induced Apoptosis by Enhancing the Interaction between p38 and Retinoblastoma Tumor Suppressor

Gadd45b Mediates Fas-induced Apoptosis by Enhancing the Interaction between p38 and Retinoblastoma Tumor Suppressor

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Identification of a Novel Endoplasmic Reticulum Stress Response Element Regulated by XBP1

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