Regulation of cellular functions by the ERK5 signalling pathway
ABSTRACT Extracellular-regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase (MAPK) regulated by a wide range of mitogens and cellular stresses. Since its cloning in 1995, the lack of biological tools, including antibodies and specific inhibitors, have made it one of the least studied MAPK subfamilies. The discovery that ERK5 was an important contributor to cell survival mechanisms has increased interest in this signalling pathway. The ability of inhibitors of the classical MAPK (ERK1/2) cascade to block ERK5 activation suggested that ERK5 might regulate some cellular functions originally attributed to ERK1/2. For example, ERK5 is suspected to mediate the effects of numerous oncogenes. A link between abnormal levels of ERK5 expression and cancers was established by the analysis of human tumours. Recently, the targeted deletions of the erk5 and the mek5 genes in mice have provided genetic evidence that the ERK5 cascade is a non-redundant signalling pathway essential for normal cardiovascular development. The analysis of genetically modified mice in which the erk5 gene can be specifically deleted in certain tissues is shedding light into the physiological function of the ERK5 pathway during development and pathogenesis.
SourceAvailable from: Yazmín Gómez-Gómez
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ABSTRACT: MicroRNAs and siRNAs belong to a family of small noncoding RNAs which bind through partial sequence complementarity to 3 í® í°-UTR regions of mRNA from target genes, resulting in the regulation of gene expression. MicroRNAs have become an attractive target for genetic and pharmacological modulation due to the critical function of their target proteins in several signaling pathways, and their expression profiles have been found to be altered in various cancers. A promising technology platform for selective silencing of cell and/or viral gene expression using siRNAs is currently in development. Cervical cancer is the most common cancer in women in the developing world and sexually transmitted infection with HPV is the cause of this malignancy. Therefore, a cascade of abnormal events is induced during cervical carcinogenesis, including the induction of genomic instability, reprogramming of cellular metabolic pathways, deregulation of cell proliferation, inhibition of apoptotic mechanisms, disruption of cell cycle control mechanisms, and alteration of gene expression. Thus, in the present review article, we highlight new research on microRNA expression profiles which may be utilized as biomarkers for cervical cancer. Furthermore, we discuss selective silencing of HPV E6 and E7 with siRNAs which represents a potential gene therapy strategy against cervical cancer.BioMed Research International 03/2015; 2015. DOI:10.1155/2015/374924 · 2.71 Impact Factor
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ABSTRACT: The current standard regimens for the treatment of acute myeloid leukemia (AML) are curative in less than half of patients; therefore, there is a great need for innovative new approaches to this problem. One approach is to target new treatments to the pathways that are instrumental to cell growth and survival with drugs that are less harmful to normal cells than to neoplastic cells. In this review, we focus on the MAPK family of signaling pathways and those that are known to, or potentially can, interact with MAPKs, such as PI3K/AKT/FOXO and JAK/STAT. We exemplify the recent studies in this field with specific relevance to vitamin D and its derivatives, since they have featured prominently in recent scientific literature as having anti-cancer properties. Since microRNAs also are known to be regulated by activated vitamin D, this is also briefly discussed here, as are the implications of the emerging acquisition of transcriptosome data and potentiation of the biological effects of vitamin D by other compounds. While there are ongoing clinical trials of various compounds that affect signaling pathways, more studies are needed to establish the clinical utility of vitamin D in the treatment of cancer.