Involvement of Nuclear Factor κB in c-Myc Induction by Tubulin Polymerization Inhibitors

Bourgarel-Rey, Véronique; Vallée, Sébastien; Rimet, Odile; Champion, Serge; Braguer, Diane; Desobry, A.; Briand, Claudette; Barra, Yves

doi:10.1124/mol.59.5.1165

Cited by 53 publications

(39 citation statements)

References 43 publications

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“…Indeed, depolymerization of microtubules leads to activation of NFκB, while microtubule stabilization by taxol has an inhibitory effect on NFκB in human cervix carcinoma HeLa S3 cells 6 . This is in agreement with the observation that vinblastine and nocodazole transactivate c-myc in epithelial mammary cells HBL100 via NFκB activation whereas taxol has no effect 7 . Moreover, the fact that microtubule disarray leads to the activation of c-jun Nterminal kinase (JNK) 8 , which in turn activates the c-jun subunit of the AP-1 transcription factor, together with the finding that activation of JNK results in phosphorylation and subsequent inactivation of rat GR 9 we hypothesise that JNK may participate in hGR activity regulation by microtubule disruption.…”

Section: Introductionsupporting

confidence: 92%

Microtubule Disarray in Primary Cultures of Human Hepatocytes Inhibits Transcriptional Activity of the Glucocorticoid Receptor via Activation of C-Jun N-Terminal Kinase

Dvořák¹,

Maurel²,

Ulrichová³

et al. 2004

BIOMED PAP

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Section: Introductionsupporting

confidence: 92%

Microtubule Disarray in Primary Cultures of Human Hepatocytes Inhibits Transcriptional Activity of the Glucocorticoid Receptor via Activation of C-Jun N-Terminal Kinase

Dvořák¹,

Maurel²,

Ulrichová³

et al. 2004

BIOMED PAP

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“…Although the hTERT promoter contains two putative NFkBbinding motifs, no DNA binding was observed (Yin et al, 2000). Therefore, NFkB may regulate hTERT expression via c-Myc because c-Myc is a downstream target of NFkB (Bourgarel-Rey et al, 2001) that upregulates hTERT transcription. It was reported previously that estrogen activates c-Myc expression, and that E-boxes in the hTERT promoter that bind cMyc/Max play additional roles in estrogen-induced transactivation of hTERT (Kyo et al, 1999c).…”

Section: Discussionmentioning

confidence: 99%

Induction of hTERT expression and phosphorylation by estrogen via Akt cascade in human ovarian cancer cell lines

et al. 2004

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We examined the mechanism by which estrogen regulates telomerase activity in Caov-3 human ovarian cancer cell lines, which express ER, to determine whether the regulation affects the expression and/or phosphorylation of the telomerase catalytic subunit (hTERT). 17b-Estradiol (E 2 ) induced telomerase activity and hTERT expression. Transient expression assays using luciferase reporter plasmids containing various fragments of hTERT promoter showed that the estrogen-responsive element appeared to be partially responsible for the E 2 -induced activation of the hTERT promoter. Either pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, or transfection with a dominantnegative Akt attenuated the E 2 -induced activation of the hTERT promoter. In addition, estrogen induced the phosphorylation of IjB inhibitor protein via the Akt cascade, and cotransfection with a dominant-negative subunit of NFjB attenuated the response of the ERE-deleted hTERT promoter to E 2 . Moreover, E 2 induced the phosphorylation of hTERT, the association of 14-3-3 protein and NFjB with hTERT, and nuclear accumulation of hTERT in an Akt-dependent manner. These results indicate that E 2 induces telomerase activity not only by transcriptional regulation of hTERT via an ERE-dependent mechanism and a PI3K/Akt/NFjB cascade, but also by post-transcriptional regulation via Akt-dependent phosphorylation of hTERT. Thus, the phosphorylation of Akt is a key event in the induction of telomerase activity by E 2 in human ovarian cancer cells.

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“…In the promoter of the proto-oncogene c-myc there are two B sites (44) indicating that NF-B can regulate c-myc. In human colon adenocarcinoma cells, vinblastine and nocodonazole, both inhibitors of tubulin polymerization, lead to NF-B activation (45). The vinblastineinduced transactivation of c-myc is partially dependent on NF-B as mutations in the B sites decrease the capacity of vinblastine to stimulate the transactivation of c-myc.…”

Section: Discussionmentioning

confidence: 99%

Low Intracellular Zinc Impairs the Translocation of Activated NF-κB to the Nuclei in Human Neuroblastoma IMR-32 Cells

Mackenzie

Zago

Keen

et al. 2002

Journal of Biological Chemistry

107

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In the current work, we studied how variations in extracellular zinc concentrations modulate different steps involved in nuclear factor B (NF-B) activation in human neuroblastoma IMR-32 cells. Cells were incubated in media containing varying concentrations of zinc (1.5, 5, 15, and 50 M). Within 3 h, the intracellular zinc content was lower in cells exposed to 1.5 and 5 M, compared with the other groups. Low intracellular zinc concentrations were associated with the activation of NF-B, based on high levels of IB␣ phosphorylation, low IB␣ concentrations, and high NF-B binding activity in total cell fractions. However, the active dimer accumulated in the cytosol, as shown by a low ratio of nuclear/cytosolic NF-B binding activity. This altered nuclear translocation was accompanied by a decreased transactivation of an endogenous NF-B-driven gene (ikba) and of a reporter gene (pNF-B-luc). In cells with low intracellular zinc concentrations, a low rate of in vitro tubulin polymerization was measured compared with the other groups. We conclude that low intracellular zinc concentrations induce tubulin depolymerization, which may be one signal for NF-B activation. However, NF-B nuclear translocation is impaired, which inhibits the transactivation of NF-B-driven genes. This could affect cell survival, and be an important factor in certain zinc deficiency-associated pathologies.

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Involvement of Nuclear Factor κB in c-Myc Induction by Tubulin Polymerization Inhibitors

Cited by 53 publications

References 43 publications

Microtubule Disarray in Primary Cultures of Human Hepatocytes Inhibits Transcriptional Activity of the Glucocorticoid Receptor via Activation of C-Jun N-Terminal Kinase

Microtubule Disarray in Primary Cultures of Human Hepatocytes Inhibits Transcriptional Activity of the Glucocorticoid Receptor via Activation of C-Jun N-Terminal Kinase

Induction of hTERT expression and phosphorylation by estrogen via Akt cascade in human ovarian cancer cell lines

Low Intracellular Zinc Impairs the Translocation of Activated NF-κB to the Nuclei in Human Neuroblastoma IMR-32 Cells

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