RAC‐3 is a NF‐κB coactivator

Werbajh, Santiago; Nojek, I M; Lanz, Rainer B.; Costas, Mónica Alejandra

doi:10.1016/s0014-5793(00)02223-7

Cited by 114 publications

(136 citation statements)

References 37 publications

(51 reference statements)

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“…The absence of a protective effect in cells untransfected with the expression vector for the co-activator was presumably due to the essentially undetectable levels of endogenous RAC3 co-activator, at least for the protein quantity that was used in western blot assays (Figure 2f). This is in agreement with the concept that limiting quantities of p160 co-activators are present in non-tumoral cells (Sheppard et al, 1998;Werbajh et al, 2000). In addition, this figure clearly shows increased expression levels of RAC3 in cells transiently transfected with the expression vector and the resulting inhibition by siRNA compared to extracts from transfected control cells overexpressing RAC3 as well as the breast tumor T47D cell line.…”

Section: Resultssupporting

confidence: 90%

“…As previously described in other cell lines (Werbajh et al, 2000), we observed that RAC3 overexpression significantly enhanced H 2 O 2 -induced NF-kB transcriptional activity in HEK293 cells as compared to cells transfected with empty vector (Figure 3a). These results raise the possibility that an increase in the transcription of anti-apoptotic NF-kB target genes could represent a mechanism by which overexpression of the RAC3 co-activator protects cells from cell death.…”

Section: Resultssupporting

confidence: 87%

“…However, these proteins have been reported to enhance the activity not only of nuclear receptors but also of a number of other transcription factors (Na et al, 1998), including nuclear factor kappa B (NF-kB), as previously described for RAC3 (Werbajh et al, 2000). Moreover, we have recently demonstrated that the latter coactivator could be found associated with a protein complex containing the estrogen receptor in addition to the transcription factor and could also regulate the expression of genes involved in cell proliferation (Rubio et al, 2006).…”

Section: Introductionmentioning

confidence: 59%

“…This is the case for NF-kB (Sheppard et al, 1999;Werbajh et al, 2000), which is a key anti-apoptotic transcription factor that controls the cell cycle and cell proliferation (Beg and Baltimore, 1996;Guttridge et al, 1999;Hinz et al, 1999). Collectively, these observations suggest that p160 co-activators may play a role in oncogenesis, possibly through mechanisms unrelated to nuclear receptor activity or hormonestimulated growth (List et al, 2001;Cavarretta et al, 2002).…”

Section: Discussionmentioning

confidence: 92%

“…Overexpression of the RAC3 co-activator contributes to the inhibition of H 2 O 2 -induced apoptosis through an enhanced NF-kB activity In view of evidence that both p160 as well as CBP/p300 are co-activators of NF-kB (Sheppard et al, 1999;Werbajh et al, 2000), the transcriptional activity of this transcription factor was analysed in HEK293 cells transfected with the expression vector for RAC3 and stimulated with H 2 O 2 . As previously described in other cell lines (Werbajh et al, 2000), we observed that RAC3 overexpression significantly enhanced H 2 O 2 -induced NF-kB transcriptional activity in HEK293 cells as compared to cells transfected with empty vector (Figure 3a).…”

Section: Resultsmentioning

confidence: 99%

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The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

et al. 2007

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The p160 nuclear receptor co-activators represent a family of molecules, which are recruited by steroid nuclear receptors as well as other transcription factors that are overexpressed in several tumors. We investigated the role of one member of this family on the sensitivity of cells to apoptosis. We observed that overexpression of the RAC3 (receptor-associated co-activator-3) p160 co-activator inhibits hydrogen peroxide-induced cell death in human embryonic kidney 293 (HEK293) cells. The mechanism involves the activation of anti-apoptotic pathways mediated through enhanced nuclear factor kappa B (NFjB) activity, inhibition of caspase-9 activation, diminished apoptotic-inducing factor (AIF) nuclear localization and a change in the activation pattern of several kinases, including an increase in both AKT and p38 kinase activities, and inhibition of ERK2. Moreover, RAC3 has been found associated with a protein complex containing AIF, Hsp90 and dynein, suggesting a role for the coactivator in the cytoplasmatic nuclear transport of these proteins associated with cytoskeleton. These results demonstrate that there are several molecular pathways that could be affected by their overexpression, including those not restricted to steroid regulation or the nuclear action of co-activators, which results in diminished sensitivity to apoptosis. Furthermore, this could represent one mechanism by which co-activators contribute to tumor development.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

et al. 2007

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Diversity in the mechanisms of gene regulation by estrogen receptors

et al. 2002

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The sequencing of the human genome has opened the way for using bioinformatics to identify sets of genes controlled by specific regulatory signals. Here, we review the unexpected diversity of DNA response elements mediating transcriptional regulation by estrogen receptors (ERs), which control the broad physiological effects of estrogens. Consensus palindromic estrogen response elements are found in only a few known estrogen target genes, whereas most responsive genes contain only low-affinity half palindromes, which may also control regulation by other nuclear receptors. ERs can also regulate gene expression in the absence of direct interaction with DNA, via protein-protein interactions with other transcription factors or by modulating the activity of upstream signaling components, thereby significantly expanding the repertoire of estrogen-responsive genes. These diverse mechanisms of action must be taken into account in screening for potential estrogen-responsive sequences in the genome or in regulatory regions of target genes identified by expression profiling.

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Protein expression and amplification of AIB1 in human urothelial carcinoma of the bladder and overexpression of AIB1 is a new independent prognostic marker of patient survival

Luo¹,

Xie²,

Liu³

et al. 2008

Intl Journal of Cancer

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AIB1, a candidate oncogene in human breast cancer, is frequently amplified and overexpressed in several types of human cancers, but the status of AIB1 amplification and expression in urothelial carcinoma of the bladder (UC) and its clinical/prognostic significance is unclear. In our study, the methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of AIB1 in 163 primary UCs and in 30 samples of normal bladder mucosa. Overexpression of AIB1 and amplification of AIB1 was found in 32.5 and 7.0% of UCs, respectively. In univariate survival analysis of the UC cohorts, a highly significant association of overexpression of AIB1 with shortened patient survival (mean: 45.6 months vs. 59.0 months, p < 0.001, log rank test) was demonstrated. In different subsets of UC patients, overexpression of AIB1 was also a prognostic indicator in grade 1 (p = 0.007), grade 2 (p = 0.010) and grade 3 (p = 0.015) tumor patients, and in pTa (p = 0.025), pT2-4 (p = 0.004), pN0 (p < 0.001) and pT2-4/pN0 (p = 0.040) tumor patients. Importantly, AIB1 expression (p < 0.001) together with pT and pN status (p < 0.05) provided significant independent prognostic parameters in multivariate analysis. In addition, a significant correlation (p < 0.05) of overexpression of AIB1 with an increased UC labeling index of Ki-67 (a cell proliferation marker) was observed in these UCs. Thus, these findings provide evidence that an overexpression of AIB1, as detected by immunohistochemistry, is an independent molecular marker for poor prognosis (shortened survival time) of patients with UC.

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RAC‐3 is a NF‐κB coactivator

Cited by 114 publications

References 37 publications

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

Diversity in the mechanisms of gene regulation by estrogen receptors

Protein expression and amplification of AIB1 in human urothelial carcinoma of the bladder and overexpression of AIB1 is a new independent prognostic marker of patient survival

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