Constitutive Expression of the AP-1 Transcription Factors c-jun, junD, junB, and c-fos and the Marginal Zone B-Cell Transcription Factor Notch2 in Splenic Marginal Zone Lymphoma

Trøen, Gunhild; Nygaard, Vigdis; Jenssen, Tor Kristian; Ikonomou, Ida Münster; Tierens, Anne; Matutes, Estella; Gruszka-Westwood, Alicja M.; Catovsky, Daniel; Myklebost, Ola; Lauritzsen, Grete F.; Hovig, Eivind; Delabie, Jan

doi:10.1016/s1525-1578(10)60525-9

Cited by 48 publications

(40 citation statements)

References 34 publications

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“…Further, on comparing expression levels of NER genes among methylated and unmethylated OSCC samples, mRNA expression of XPB gene was found to be significantly decreased in methylated samples as compared to unmethylated samples, confirming an inverse relation between methylation and gene expression and supporting the earlier reports showing methylation to repress gene expression [25,26]. Promoter methylation of XPC and XPD genes was not found to regulate the expression of these genes in our study thereby suggesting the involvement of alternative mechanisms [copy number variations, transcription factor production and recruitment, histone modifications and microRNA expression] in regulation of their gene expression.…”

Section: Expression Of Ner Pathway Genes In Osccsupporting

confidence: 83%

Spectrophotometric Determination of Nifedipine and Nicardipine in their Pharmaceutical Preparations

Hamd¹,

Abdellatif²

2015

Ind Chem

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Genotoxic exposure to tobacco carcinogens resulting in DNA damage is an important mechanism of oral squamous cell carcinoma (OSCC) etiology. Nucleotide Excision Repair (NER) pathway removes bulky DNA adducts, generated from tobacco exposure thereby playing a major role in initiation of OSCC. In addition to mutations, epigenetic modifications have also been shown to target DNA repair genes thereby modulating oral tumor genesis. We therefore examined the role of epigenetic alterations modulating expression of three NER genes; XPC, XPB and XPD involved in removal of adducts caused by major classes of tobacco carcinogens and their contribution to OSCC Methylation status of NER genes was assessed using methylation specific PCR (MSP) in biopsies taken from 52 OSCC patients, their surrounding margins and 27 normal controls. The mRNA levels were determined using quantitative real time PCR (qRT-PCR) and Chromatin immuno precipitation (ChIP) analysis was performed to examine histone modifications in selected NER genes.We did not observe any significant difference in promoter methylation of NER genes between OSCC patients and controls. Increased XPB mRNA levels (p 0.04) and higher prevalence of H3 acetylation of XPB (p 0.04) gene were observed in OSCC patients as compared to controls.Our findings suggest the epigenetic modifications regulating the expression of XPB gene may be involved in OSCC etiology.

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Section: Expression Of Ner Pathway Genes In Osccsupporting

confidence: 83%

Spectrophotometric Determination of Nifedipine and Nicardipine in their Pharmaceutical Preparations

Hamd¹,

Abdellatif²

2015

Ind Chem

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“…These findings are consistent with the cell survival role of JNK upon loss of DUSP4 in DLBCL (35), the known transformational potential of c-Jun (reviewed in refs. 18 and 36), and the aberrant activities of JNK and AP-1 signaling that are frequently observed in other human Hodgkin's and non-Hodgkin's lymphomas, in which they induce proliferation and suppress apoptosis (4,(37)(38)(39)(40)(41). How dysregulated CBM complexes couple mechanistically to the JNK pathway is still an open question.…”

Section: Discussionmentioning

confidence: 99%

Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation

Knies

Alankus

Weilemann

et al. 2015

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

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The aggressive activated B cell-like subtype of diffuse large B-cell lymphoma is characterized by aberrant B-cell receptor (BCR) signaling and constitutive nuclear factor kappa-B (NF-κB) activation, which is required for tumor cell survival. BCR-induced NF-κB activation requires caspase recruitment domain-containing protein 11 (CARD11), and CARD11 gain-of-function mutations are recurrently detected in human diffuse large B-cell lymphoma (DLBCL). To investigate the consequences of dysregulated CARD11 signaling in vivo, we generated mice that conditionally express the human DLBCL-derived CARD11(L225LI) mutant. Surprisingly, CARD11(L225LI) was sufficient to trigger aggressive B-cell lymphoproliferation, leading to early postnatal lethality. CARD11(L225LI) constitutively associated with B-cell CLL/lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) to simultaneously activate the NF-κB and c-Jun N-terminal kinase (JNK) signaling cascades. Genetic deficiencies of either BCL10 or MALT1 completely rescued the phenotype, and pharmacological inhibition of JNK was, similar to NF-κB blockage, toxic to autonomously proliferating CARD11(L225LI)-expressing B cells. Moreover, constitutive JNK activity was observed in primary human activated B cell-like (ABC)-DLBCL specimens, and human ABC-DLBCL cells were also sensitive to JNK inhibitors. Thus, our results demonstrate that enforced activation of CARD11/BCL10/MALT1 signaling is sufficient to drive transformed B-cell expansion in vivo and identify the JNK pathway as a therapeutic target for ABC-DLBCL.

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“…Abnormal levels of steady state junD mRNA and JunD protein have been reported in many types of cancer cells and in response to hormones and other factors (Table 2; Neyns et al, 1996;Pollack et al, 1997;Li et al, 2002a, b;Troen et al, 2004). Some studies solely measured the abundance of JunD protein.…”

Section: Jund Is a Central Molecule In An Intricate Regulatory Networkmentioning

confidence: 99%

Multiple facets of junD gene expression are atypical among AP-1 family members

et al. 2008

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JunD is a versatile AP-1 transcription factor that can activate or repress a diverse collection of target genes. Precise control of junD expression and JunD proteinprotein interactions modulate tumor angiogenesis, cellular differentiation, proliferation and apoptosis. Molecular and clinical knowledge of two decades has revealed that precise JunD activity is elaborated by interrelated layers of constitutive transcriptional control, complex post-transcriptional regulation and a collection of post-translational modifications and protein-protein interactions. The stakes are high, as inappropriate JunD activity contributes to neoplastic, metabolic and viral diseases. This article deconvolutes multiple layers of control that safeguard junD gene expression and functional activity. The activity of JunD in transcriptional activation and repression is integrated into a regulatory network by which JunD exerts a pivotal role in cellular growth control. Our discussion of the JunD regulatory network integrates important open issues and posits new therapeutic targets for the neoplastic, metabolic and viral diseases associated with JunD/AP-1 expression.

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Constitutive Expression of the AP-1 Transcription Factors c-jun, junD, junB, and c-fos and the Marginal Zone B-Cell Transcription Factor Notch2 in Splenic Marginal Zone Lymphoma

Cited by 48 publications

References 34 publications

Spectrophotometric Determination of Nifedipine and Nicardipine in their Pharmaceutical Preparations

Spectrophotometric Determination of Nifedipine and Nicardipine in their Pharmaceutical Preparations

Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation

Multiple facets of junD gene expression are atypical among AP-1 family members

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