Search results for "translation"

2018

RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under…

Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency

2018

In response to iron deficiency, the budding yeast Saccharomyces cerevisiae undergoes a metabolic remodeling in order to optimize iron utilization. The tandem zinc finger (TZF)-containing protein Cth2 plays a critical role in this adaptation by binding and promoting the degradation of multiple mRNAs that contain AU-rich elements (AREs). Here, we demonstrate that Cth2 also functions as a translational repressor of its target mRNAs. By complementary approaches, we demonstrate that Cth2 protein inhibits the translation of SDH4, which encodes a subunit of succinate dehydrogenase, and CTH2 mRNAs in response to iron depletion. Both the AREs within SDH4 and CTH2 transcripts, and the Cth2 TZF are es…

Spanish Cell Therapy Network (TerCel): 15 years of successful collaborative translational research

2019

On behalf of TerCel

Nut1/Hos1 and Sas2/Rpd3 control the H3 acetylation of two different sets of osmotic stress-induced genes

2019

Epigenetic information is able to interact with the cellular environment and could be especially useful for reprograming gene expression in response to a physiological perturbation. In fact the genes induced or repressed by osmotic stress undergo significant changes in terms of the levels of various histone modifications, especially in the acetylation levels of histone H3. Exposing yeast to high osmolarity results in the activation of stress-activated protein kinase Hog1, which plays a central role in gene expression control. We evaluated the connection between the presence of Hog1 and changes in histone H3 acetylation in stress-regulated genes. We found a parallel increase in the acetylati…

The organoid era permits the development of new applications to study glioblastoma

2020

Simple Summary Glioblastoma is the most lethal primary adult brain tumor. The great number of mutations involved and the aggressiveness of glioblastoma render this type of cancer especially difficult to investigate. To address this problem, cerebral organoids have emerged as promising tools to investigate brain biology and to recapitulates the major steps involved in glioblastoma tumorigenesis. This review focuses on methods of cerebral organoid development, describes the protocols used for inducing glioblastoma, the approach used to derive glioblastoma organoids directly from patients’ biopsies and discusses their limitations and potential future direction. Abstract Glioblastoma (GB) is th…

Personalized Medicine: Recent Progress in Cancer Therapy

2020

Translational research has revolutionized how we develop new treatments for cancer patients. The change from an organ-centric concept guiding treatment choice towards deep molecular analysis, driving a personalized approach, is one of the most important advances of modern oncology. Several tools such as next generation sequencing and RNA sequencing have greatly improved the capacity to detect predictive and prognostic molecular alterations. Detection of gene mutations, amplifications, and fusions has therefore altered the history of several diseases in both a localized and metastatic setting. This shift in perspective, in which attention is focused on the specific molecular alterations of t…

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma : the oncogenic role of the ligands

2017

Altres ajuts: This work was supported by grants from Institut Català d'Oncologia (ICO), Instituto de Salud Carlos III (RTICC-RD12/0036/0016, /0020, /0035, /0057; and PI14/00647), Fundació A BOSCH, Fundació Amics Joan Petit, ajuts predoctorals del VHIR and RIS3CAT grants COMRDI15-1-0014 (ACCIÓ and FEDER). Altres ajuts: FEDER/COMRDI15-1-0014 Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional …

Mcl-1 targeting could be an intriguing perspective to cure cancer

2018

The Bcl-2 family, which plays important roles in controlling cancer development, is divided into antiapoptotic and proapoptotic members. The change in the balance between these members governs the life and death of the cells. Mcl-1 is an antiapoptotic member of this family and its distribution in normal and cancerous tissues strongly differs from that of Bcl-2. In human cancers, where upregulation of antiapoptotic proteins is common, Mcl-1 expression is regulated independent of Bcl-2 and its inhibition promotes senescence, a major barrier to tumorigenesis. Cancer chemotherapy determines various kinds of responses, such as senescence and autophagy; however, the ideal response to chemotherapy…

Role of TCTP for Cellular Differentiation and Cancer Therapy

2017

The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein. In this article, we draw attention to the …

Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice

2020

Abstract Background Conventional type 1 dendritic cells (cDC1s) control anti‐viral and anti‐tumor immunity by inducing antigen‐specific cytotoxic CD8+ T‐cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF‐κB, might determine the precise outcome of Th‐cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2‐driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF‐κB signaling. Methods To target pulmonary cDC1s, Cd207 (Lan…