Myeloid differentiation (MyD) primary response genes in hematopoiesis

Liebermann, Dan A.; Hoffman, Barbara

doi:10.1038/sj.onc.1205312

Cited by 66 publications

(70 citation statements)

References 162 publications

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“…Notwithstanding, IRF-1 has been implicated as a mediator for interferon signaling, when induced by TNF-α, interferons, viral infections and retinoids. IRF-1 has been considered to be a TSG that plays an essential role in cell growth control and surveillance against malignant development (13). The findings of the present study support the view of IRF-1 as an important TSG.…”

supporting

confidence: 80%

Association of loss of heterozygosity with cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Pinheiro

Serio

Silva

et al. 2008

Braz J Med Biol Res

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Deletions on chromosomes 5 and 7 are frequently seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is assumed that these deletions indicate loss of tumor suppressor genes on these chromosomes and until these tumor suppressor genes are identified, the functional consequences of these deletions and the molecular basis of these myeloid disorders cannot be completely understood. We evaluated loss of heterozygosity (LOH) in 44 patients (18 MDS and 26 AML, diagnosed according to WHO classification criteria) at diagnosis, using a four-microsatellite marker panel: an intragenic marker on the 7th intron of gene IRF-1 of the 5q31.1 region and three markers located inside the 7q31.1 region and correlated the LOH with karyotype abnormalities. The microsatellites chosen corresponded to chromosome regions frequently deleted in MDS/ AML. The samples with Q (peak area) less than or equal to 0.50 were indicative of LOH. The percent of informative samples (i.e., heterozygous) for the intragenic microsatellite in gene IRF-1 and in loci D7S486, D7S515 and D7S522 were 66.6, 73.7, 75.5, and 48.8%, respectively. Cytogenetic abnormalities by G-banding were found in 36% (16/44) of the patients (2 of 18 MDS and 14 of 26 AML patients). We found a significantly positive association of the occurrence of LOH with abnormal karyotype (P < 0.05; chisquare test) and there were cases with LOH but the karyotype was normal (by G-banding). These data indicate that LOH in different microsatellite markers is possibly an event previous to chromosomal abnormalities in these myeloid neoplasias.

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supporting

confidence: 80%

Association of loss of heterozygosity with cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Pinheiro

Serio

Silva

et al. 2008

Braz J Med Biol Res

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“…In many instances, the biological activity of Gadd45 factors has been linked to regulation of protein kinases, such as MAPK pathway kinases (15)(16)(17). We showed for instance that Gadd45␤ binds directly to MKK7, and that this binding is sufficient alone to cause inactivation of this kinase.…”

mentioning

confidence: 88%

“…Contacting MKK7-Gadd45 proteins have no known enzymatic activity (16,17). Thus, to determine the basis for Gadd45␤-mediated inactivation of MKK7, we mapped the region(s) of Gadd45␤ involved in interaction with this kinase.…”

Section: Identification Of the Regions Of Gadd45␤mentioning

confidence: 99%

“…We showed for instance that Gadd45␤ binds directly to MKK7, and that this binding is sufficient alone to cause inactivation of this kinase. As other Gadd45 family proteins, however, Gadd45␤ lacks enzymatic activity such as phosphatase activity (16,17), and so, the basis for its ability to block MKK7 remains unknown. To understand this basis, here we used a combined structural and functional approach.…”

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confidence: 99%

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Insights into the Structural Basis of the GADD45β-mediated Inactivation of the JNK Kinase, MKK7/JNKK2

Papa

Monti

Vitale

et al. 2007

Journal of Biological Chemistry

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NF-B/Rel factors control programmed cell death (PCD), and this control is crucial to oncogenesis, cancer chemoresistance, and antagonism of tumor necrosis factor (TNF) ␣-induced killing. With TNF␣, NF-B-mediated protection involves suppression of the c-Jun-N-terminal kinase (JNK) cascade, and we have identified Gadd45␤, a member of the Gadd45 family, as a pivotal effector of this activity of NF-B. Inhibition of TNF␣-induced JNK signaling by Gadd45␤ depends on direct targeting of the JNK kinase, MKK7/JNKK2. The mechanism by which Gadd45␤ blunts MKK7, however, is unknown. Here we show that Gadd45␤ is a structured protein with a predicted four-stranded ␤-sheet core, five ␣-helices, and two acidic loops. Association of Gadd45␤ with MKK7 involves a network of interactions mediated by its putative helices ␣3 and ␣4 and loops 1 and 2. Whereas ␣3 appears to primarily mediate docking to MKK7, loop 1 and ␣4-loop 2 seemingly afford kinase inactivation by engaging the ATP-binding site and causing conformational changes that impede catalytic function. These data provide a basis for Gadd45␤-mediated blockade of MKK7, and ultimately, TNF␣-induced PCD. They also have important implications for treatment of widespread diseases.

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“…Gadd45b (which encodes growth arrest and DNAdamage-inducible 45β), Gadd45a and Gadd45g are members of the Gadd45 gene family, which is involved in growth arrest, apoptosis and DNA repair [21]. We have recently shown that overexpression of Gadd45b downregulates pro-apoptotic JNK signalling in mouse embryo fibroblasts (MEFs) and 3DO T cells, without affecting the ERK and p38 activities [22].…”

Section: Introductionmentioning

confidence: 99%

Growth arrest- and DNA-damage-inducible 45β gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1β-induced apoptosis in insulin-producing INS-1E cells

et al. 2006

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Aims/hypothesis: IL-1β is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1β activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen-activated protein kinase (MAPK) family. Inhibition of JNK prevents IL-1β-mediated beta cell destruction. In mouse embryo fibroblasts and 3DO T cells, overexpression of the gene encoding growth arrest and DNA-damage-inducible 45β (Gadd45b) downregulates pro-apoptotic JNK signalling. The aim of this study was to investigate if Gadd45b prevents IL-1β-induced beta cell MAPK signalling and apoptosis. Materials: Rat insulinoma INS-1E cells and mouse beta-TC3 cells stably expressing Gadd45b were generated. The effects of Gadd45b expression on signalling by JNK, ERK and p38 were assessed by Western blotting and kinase assays. Apoptosis rate was measured by terminal deoxynucleotidyl-mediated dUTP-biotin nick end-labelling (TUNEL) and an ELISA designed to detect apoptotic nucleosomes. Expression of endogenous Gadd45b mRNA was measured by RT-PCR. Results: In INS-1E and beta-TC3 cells, expression ofGadd45b inhibited IL-1β-induced activation of JNK and ERK, but augmented IL-1β-mediated p38 activity. IL-1β-induced nitric oxide production and decreases in insulin content and secretion were reduced by GADD45β. IL-1β-induced apoptosis was reduced by GADD45β by up to 77%. Although IL-1β stimulated the time-dependent induction of endogenous Gadd45b in INS-1E cells and rat islets, expression levels were lower in these cells than in IL-1β-exposed NIH-3T3 and 3DO T cells.

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Myeloid differentiation (MyD) primary response genes in hematopoiesis

Cited by 66 publications

References 162 publications

Association of loss of heterozygosity with cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Association of loss of heterozygosity with cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Insights into the Structural Basis of the GADD45β-mediated Inactivation of the JNK Kinase, MKK7/JNKK2

Growth arrest- and DNA-damage-inducible 45β gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1β-induced apoptosis in insulin-producing INS-1E cells

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