Identification of the distinct promoters for the two transcripts of apoptosis related protein 3 and their transcriptional regulation by NFAT and NFκB
Department of Biochemistry and Molecular Biology, State Key Lab of Cancer Biology, Fourth Military Medical University, Xi'an 710032, P.R. China. Molecular and Cellular Biochemistry
(Impact Factor: 2.39).
09/2007; 302(1-2):187-94. DOI: 10.1007/s11010-007-9440-7
APR3 (apoptosis related protein 3) is a novel gene highly conserved across species. Analysis of the data about APR3 available at GEO profiles revealed consistent and significant changes of APR3 expression level in certain developmental and inflammatory processes. Based on the search and analysis of all the submitted mRNA sequence, we postulated that the two transcripts may arise from separate promoter activities rather than previously assumed alternative splicing. Through reporter assay and PCR data, we identified the distinct promoters for the two transcripts of APR3. Furthermore, exogenous expression of a constitutively active mutant of transcription factor NFAT was able to enhance both the promoter activities of APR3. Sequential deletion of the promoter from the 5' side and mutation of the promoter suggested the functional NFAT binding sites might localize between -96 bp and -47 bp. In contrast, exogenous expression of a constitutively active mutant of the transcription factor NFkB inhibited APR3 transcription. Our data suggested that APR3 might be functionally important in certain processes under which NFAT and/or NFkappaB are/is activated.
Available from: Abu Hasanat Md. Zulfiker
- "NF-κB is considered the “master” gene transcription factor for promoting inflammation by regulating proinflammatory mediators. On the other hand, NF-κB itself is activated by these same inflammatory cytokines [32, 33]. Studies in mouse models show that NF-κB and TNF-α are linked with cancer progression [34, 35]. "
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ABSTRACT: Toad glandular secretions and skin extractions contain many natural agents which may provide a unique resource for novel drug development. The dried secretion from the auricular and skin glands of Chinese toad (Bufo bufo gargarizans) is named Chansu, which has been used in Traditional Chinese Medicine (TCM) for treating infection and inflammation for hundreds of years. The sterilized hot water extraction of dried toad skin is named Huachansu (Cinobufacini) which was developed for treating hepatitis B virus (HBV) and several types of cancers. However, the mechanisms of action of Chansu, Huachansu, and their constituents within are not well reported. Existing studies have suggested that their anti-inflammation and anticancer potential were via targeting Nuclear Factor (NF)-κB and its signalling pathways which are crucial hallmarks of inflammation and cancer in various experimental models. Here, we review some current studies of Chansu, Huachansu, and their compounds in terms of their use as both anti-inflammatory and anticancer agents. We also explored the potential use of toad glandular secretions and skin extractions as alternate resources for treating human cancers in combinational therapies.
Evidence-based Complementary and Alternative Medicine 03/2014; 2014:312684. DOI:10.1155/2014/312684 · 1.88 Impact Factor
Available from: Inmaculada Posadas
- "However, the role of NFkB in apoptosis is complex. Both apoptosis suppression – and induction – have been reported. Thus, many atypical inducers of NFkB such as UV radiation, H2O2 and some anticancer drugs have been associated with the proapoptotic function of NFkB . "
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ABSTRACT: Neuroblastoma resistance to apoptosis may contribute to the aggressive behavior of this tumor. Therefore, it would be relevant to activate endogenous cellular death mechanisms as a way to improve neuroblastoma therapy. We used the neuroblastoma SH-SY5Y cell line as a model to study the mechanisms involved in acetaminophen (AAP)-mediated toxicity by measuring CYP2E1 enzymatic activity, NFkB p65 subunit activation and translocation to the nucleus, Bax accumulation into the mitochondria, cytochrome c release and caspase activation. AAP activates the intrinsic death pathway in the SH-SY5Y human neuroblastoma cell line. AAP metabolism is partially responsible for this activation, because blockade of the cytochrome CYP2E1 significantly reduced but did not totally prevent, AAP-induced SH-SY5Y cell death. AAP also induced NFkB p65 activation by phosphorylation and its translocation to the nucleus, where NFkB p65 increased IL-1β production. This increase contributed to neuroblastoma cell death through a mechanism involving Bax accumulation into the mitochondria, cytochrome c release and caspase3 activation. Blockade of NFkB translocation to the nucleus by the peptide SN50 prevented AAP-mediated cell death and IL-1β production. Moreover, overexpression of the antiapoptotic protein Bcl-x(L) did not decrease AAP-mediated IL-1β production, but prevented both AAP and IL-1β-mediated cell death. We also confirmed the AAP toxic actions on SK-N-MC neuroepithelioma and U87MG glioblastoma cell lines. The results presented here suggest that AAP activates the intrinsic death pathway in neuroblastoma cells through a mechanism involving NFkB and IL-1β.
PLoS ONE 11/2012; 7(11):e50160. DOI:10.1371/journal.pone.0050160 · 3.23 Impact Factor
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ABSTRACT: The electrical transport properties of C<sub>70</sub> and C<sub>60</sub> fullerene peapods are investigated. We report the fabrications and performances of field-effect transistors (FETs) based on C<sub>70</sub> and C<sub>60</sub> fullerene peapods. Most of the fullerene peapod-FETs exhibit ambipolar characteristics at room temperature in air. The origin of ambipolar behavior is also qualitatively discussed. The ambipolar FETs based on fullerene peapods exhibit hysteresis effect in their electrical characteristics.
Solid-State and Integrated Circuits Technology, 2004. Proceedings. 7th International Conference on; 11/2004
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