1,721,169 research outputs found
CALRETICULIN ENHANCES THE TRANSCRIPTIONAL ACTIVITY OF THYROID TRANSCRIPTION FACTOR-1 BY BINDING TO ITS HOMEODOMAIN.
No full textCALRETICULIN ENHANCES THE TRANSCRIPTIONAL ACTIVITY OF THYROID TRANSCRIPTION FACTOR-1 BY BINDING TO ITS HOMEODOMAIN.
No full textEmerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology
No full textOnco-microRNAs (onco-miRNAs) are essential players in the post-transcriptional regulation of gene expression and exert a crucial role in tumorigenesis. Novel information about the epitranscriptomic modifications, involved in onco-miRNAs biogenesis, and in the modulation of their interplay with regulatory factors responsible for their processing and sorting are emerging. In this review, we highlight the contribution of bases modifications, sequence motifs, and secondary structures on miRNAs processing and sorting. We focus on several modes of action of RNA binding proteins (RBPs) on these processes. Moreover, we describe the new emerging scenario that shows an unexpected though essential role of selected DNA repair proteins in actively participating in these events, highlighting the original intervention represented by the non-canonical functions of Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), a central player in Base Excision Repair (BER) pathway of DNA lesions. Taking advantage of this new knowledge will help in prospecting new cancer diagnostic and therapeutic strategies
Redox state, oxidative stress and molecular mechanisms of protective and toxic effects of bilirubin on cells
No full textUnconjugated bilirubin (UCB) is the major degradation product of the heme catabolism. UCB is a potent antioxidant molecule as well as an indirect pro-oxidant generator. Growing evidence suggests that its major cellular effects are mediated by inhibiting proliferation in cancer cell lines and eliciting cytotoxicity, particularly in neurons and glial cells. Here we describe studies showing that alteration of the redox status and generation of oxidative stress are likely early events responsible for UCB-induced cytotoxicity. We then elucidate some of the molecular pathways that govern these effects
H2O2 modulates purinergic-dependent calcium signalling in osteoblast-like cells
No full textReactive oxygen species (ROS) have long been considered as toxic by-products of aerobic metabolism and appear involved in the pathogenesis
of degenerative diseases. The physiological role of ROS as second messengers in cell signal transduction is, on the other hand,
increasingly recognized. Here we investigated the effects of H2O2 and extracellular nucleotides on calcium signalling in four osteoblastic cell
lines. In the highly differentiated HOBIT cells, sensitive to nanomolar concentrations of ADP and UTP, millimolar H2O2 induced oscillatory
increases of the cytosolic calcium concentration followed by a steady and sustained calcium increase. Long lasting rhythmic calcium activity
was induced by micromolar H2O2 doses. The H2O2-induced calcium signals, due to both release from intracellular stores and influx from the
extracellular milieu, were totally prevented by incubating the cells with the P2 receptor antagonist suramin or with the ATP/ADP hydrolyzing
enzyme apyrase. In the osteosarcoma SaOS-2 cells micromolar H2O2 failed to evoke calcium signals and millimolar H2O2 induced a slowly
developing calcium influx which was unaffected by suramin and apyrase. These cells responded to micromolar concentrations of ATP and
ADP, but were largely insensitive to UTP. ROS 17/2.8 osteosarcoma cells were totally insensitive to ATP, ADP and UTP in keeping with
the evidence that these cells lack functional purinergic receptors. In these cells, H2O2 up to 1mM did not increase the cytosolic calcium
concentration. In ROS/P2Y2 cells, stably expressing the P2Y2 receptor, spontaneous calcium oscillations were observed in 38% of the population
and nanomolar concentration of extracellular ATP or UTP activated oscillations in quiescent cells. Spontaneous calcium signals were
inhibited by suramin and apyrase. In these cells H2O2 induced oscillatory calcium activity that was blocked by suramin and apyrase. The
sensitivity of ROS/P2Y2 cells to UTP decreased significantly in the presence of DTT, which was effective also in inhibiting spontaneous
calcium oscillations. On the other hand, the membrane-impermeant thiol oxidant DTNB induced calcium oscillations that were inhibited
by incubating the cells with suramin or apyrase. Since peroxide did not increase extracellular ATP in these cell lines, we propose that, in
osteoblasts, mild oxidative conditions could activate purinergic signalling through the sensitization of P2Y2 receptor
A chicken hnRNP of the A/B family recognizes the single-stranded d(CCCTAA)n telomeric repeated motif
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Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons
Full text linkAPE1 is an essential endodeoxyribonuclease of the base excision repair pathway that maintains genome stability. It was identified as a pivotal factor favoring tumor progression and chemoresistance through the control of gene expression by a redox-based mechanism. APE1 is overexpressed and serum-secreted in different cancers, representing a prognostic and predictive factor and a promising non-invasive biomarker. Strategies directly targeting APE1 functions led to the identification of inhibitors showing potential therapeutic value, some of which are currently in clinical trials. Interestingly, evidence indicates novel roles of APE1 in RNA metabolism that are still not fully understood, including its activity in processing damaged RNA in chemoresistant phenotypes, regulating onco-miRNA maturation, and oxidized RNA decay. Recent data point out a control role for APE1 in the expression and sorting of onco-miRNAs within secreted extracellular vesicles. This review is focused on giving a portrait of the pros and cons of the last two decades of research aiming at the identification of inhibitors of the redox or DNA-repair functions of APE1 for the definition of novel targeted therapies for cancer. We will discuss the new perspectives in cancer therapy emerging from the unexpected finding of the APE1 role in miRNA processing for personalized therapy
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