The orphan receptor ERRα interferes with steroid signaling

The estrogen receptor-related receptor α (ERRα) is an orphan member of the nuclear receptor superfamily that has been shown to interfere with the estrogen-signaling pathway. In this report, we demonstrate that ERRα also cross-talks with signaling driven by other steroid hormones. Treatment of human prostatic cells with a specific ERRα inverse agonist reduces the expression of several androgen-responsive genes, in a manner that does not involve perturbation of androgen receptor expression or activity. Furthermore, ERRα activates the expression of androgen response elements (ARE)-containing promoters, such as that of the prostate cancer marker PSA, in an ARE-dependent manner. In addition, promoters containing a steroid response element can be activated by all members of the ERR orphan receptor subfamily, and this, even in the presence of antisteroid compounds

TGF-beta 1 modulates Fas (APO-1/CD95)-mediated apoptosis of human pre-B cell lines

International audienceWe have previously shown that Fas-induced apoptosis is markedly enhanced by IL-7 in human pre-B but not pro-B cell lines. In addition, pre-B cell receptor (pre-BCR) ligation significantly potentiates the IL-7 effects on Fas-triggered pre-B cell death. We show herein that transforming growth factor (TGF)-beta1 sharply reduces Fas-induced death rate of pre-B but not pro-B cells. TGF-beta1 causes inhibition of Fas-mediated disruption of mitochondrial transmembrane potential and cleavage of caspase 8, Bid and caspase 3. Bcl2 expression is markedly increased in TGF-beta1-treated pre-B cells, whereas cellular FLICE-like inhibitory protein long (c-FLIPL), Bcl-XL, Bax, and Bad expression remains unchanged. TGF-beta1 causes a selective growth arrest of pre-B cells in G0/G1 phase of the cell cycle and induces a partial down-modulation of both Fas and pre-BCR expression. All TGF-beta1-mediated effects, but Bcl2 up-regulation, can be reproduced by the LY294002 phosphatidylinositol 3-kinase (Pl3K)/Akt inhibitor but not by inhibitors of the MAPK/ERK (MEK) and Janus kinase (Jak)/STAT pathways, which promote cell death. Akt phosphorylation is strongly inhibited by TGF-beta1 in pre-B but not pro-B cells and is not modified by Fas engagement. Altogether, our findings suggest that TGF-beta1 prevents Fas-induced apoptosis of pre-B lines by inhibiting Pl3K pathway and by enhancing expression of Bcl2. They also suggest that the Pl3K/Akt pathway is involved in the control of Fas and pre-BCR expression, a checkpoint in B cell development

POLÍTICAS DE EDUCAÇÃO CORPORATIVA E O PROCESSO DE CERTIFICAÇÃO BANCÁRIA: DISTINTOS ATORES E PERSPECTIVAS

RESUMO As iniciativas de educação corporativa vêm se institucionalizando como elemento de competitividade entre países (LANVIN; EVANS, 2013), organizações (EBOLI et al. 2010) e indivíduos (SARSUR, 2010). Como parte do resultado da melhor estruturação da educação corporativa, a qualificação da mão de obra traz no seu bojo os processos de certificação profissional. Neste contexto, o sistema financeiro brasileiro revela instituições mais efetivas na intermediação financeira e na geração de resultados, lastreadas em ações de educação corporativa e políticas de gestão de pessoas. O presente artigo delineia esta perspectiva analisando o movimento de certificação de trabalhadores bancários no Brasil, sob a égide de atores distintos como o órgão regulador; os bancos e suas universidades corporativas; as certificadoras; os sindicatos e os bancários. Verificaram-se por meio de pesquisa qualitativa de cunho descritivo, utilizando-se como instrumentos de coleta de dados a análise documental, entrevistas e grupo de foco, as políticas de gestão de pessoas sob o escopo da educação corporativa e o processo de certificação bancária sob a perspectiva destes atores. Os principais achados indicam que o Banco Central do Brasil normatiza o mercado, os bancos induzem ao processo de certificação bancária como mecanismo de ampliação de competitividade e pressão sobre o indivíduo enquanto trabalhador, e por sua vez os sindicatos atuam como coadjuvantes no processo

Voxel-based evidence of perfusion normalization in glioblastoma patients included in a phase I\textendashII trial of radiotherapy/tipifarnib combination

International audienc

Evidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells

International audienceSTAT5 transcription factors are involved in normal B lymphocyte development and in leukemogenesis. We show that the inhibition of STAT5A expression or activity in the NALM6, 697 and Reh leukemic pre-B cell lines, results in a higher spontaneous apoptosis and an increased FAS-induced cell death. However, the molecular mechanisms underlying the altered pre-B cell survival are unclear. We used a proteomic approach to identify proteins that are differentially regulated in cells expressing (NALM6Δ5A) or not a dominant negative form of STAT5A. Among the 14 proteins identified, six were involved in the control of the oxidative stress like glutathione (GSH) synthetase and DJ-1. Accordingly, we showed increased levels of reactive oxygen species (ROS) in NALM6Δ5A cells and suppression of the increased sensitivity to Fas-mediated apoptosis by the GSH tripeptide. Similar results were observed when NALM6 cells were treated with TAT-STAT5Δ5A fusion proteins or STAT5A shRNA. In addition, the 697 and Reh pre-B cells were found to share number of molecular changes observed in NALM6Δ5A cells including ROS generation, following inhibition of STAT5 expression or function. Our results point out to a hitherto undescribed link between STAT5 and oxidative stress and provide new insights into STAT5 functions and their roles in leukemogenesis