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  • mutations in exon
  • Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL). (wikipedia.org)
  • The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop. (wikipedia.org)
  • degradation
  • Slc39a8 encodes a divalent metal cation importer that has been implicated in ECM degradation through the zinc/metal regulatory transcription factor 1 (Zn/MTF1) axis, which promotes the expression of ECM-degrading enzymes, including Adamts metalloproteinases. (jci.org)
  • Ji-Yoon Noh and colleagues at the Children's Hospital of Philadelphia developed a protocol that restores endogenous GATA1 levels in MEPs derived from murine ES cells in which Gata1 mRNA is inducibly targeted for degradation, resulting in the generation of megakaryocytes capable of platelet generation. (jci.org)
  • Here, we engineered ES cells from WT mice to express a doxycycline-regulated (dox-regulated) shRNA that targets Gata1 transcripts for degradation. (jci.org)
  • Thus, LAQ824 depletes Her-2 through two mechanisms: attenuation of its mRNA levels and promotion of its degradation by the proteasome. (aacrjournals.org)
  • concomitant
  • This suggests that the "default" lineages for the hematopoietic system lean toward the innate immune system, and that lineage commitment occurs upon both the upregulation and activation of a lineage specific gene network with the concomitant downregulation or suppression of transcription of genes associated with alternative cell lineages. (blogspot.com)
  • gene expression
  • It is simpler to hypothesize that differences in mRNA-specific rates of initiation and changes in ribosome concentration can adequately explain much (if not all) of the diversity of gene expression changes in different tissues as a result of ribosomal mutations. (sciencemag.org)
  • Transcriptional regulation of gene expression in eukaryotes in response to developmental and other environmental signals is a multi-step process that requires the concerted action of many cellular factors. (biologists.org)
  • leukemogenesis
  • BCR-ABL and CCND3 BCR (breakpoint cluster region)-ABL (c-abl oncogene 1, non-receptor tyrosine kinase)/GATA1/miR-138 mini circuitry contributes to the leukemogenesis of chronic myeloid leukemia (CML). (wikipedia.org)
  • mechanisms
  • Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. (jci.org)
  • They showed that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo. (wikipedia.org)
  • miRNAs
  • The recognition of mRNA target sites, which are often located in the 3′ untranslated region (3′-UTR), by miRNAs is believed to be primarily mediated by base pairing between nucleotides 2-8 of the miRNA, a region also referred to as the seed sequence, and the cognate mRNA sequence (reviewed by Bartel, 2009 ). (biologists.org)
  • miRNA-mediated gene regulatory networks are rather complex because a single miRNA can recognize hundreds of targets and a single mRNA can be simultaneously regulated by multiple miRNAs. (biologists.org)
  • On the contrary, its precursor, pre-miR-138-2, is ubiquitously expressed throughout all tissues, which suggests that the expression of miRNAs can be regulated at the post-transcription level. (wikipedia.org)
  • mice
  • In this work, we show that mice with liver-specific triple FoxO knockout (L-FoxO1,3,4), which are known to have reduced hepatic glucose production, also have increased HDL-C. This was associated with decreased expression of the HDL-C clearance factors scavenger receptor class B type I (SR-BI) and hepatic lipase and defective selective uptake of HDL cholesteryl ester by the liver. (jci.org)
  • regulate
  • They regulate mRNA stability and consequently protein production by recruiting the RNA-induced silencing complex (RISC) to its cognate target sites. (biologists.org)
  • It has been experimentally verified that miR-138 can negatively regulate aldh1a2, encoding retinoic acid (RA) dehydrogenase (Raldh2), by targeting the binding site in the 3'UTR of its mRNA. (wikipedia.org)
  • expression
  • As fatty liver disease progresses, ACLP expression is enhanced via activation of STAT3 signaling by obesity-related factors in serum. (jci.org)
  • For example, forced expression of the anti-apoptoptic factor Bcl2 increases HSC self-renewal and transplantation efficiency. (blogspot.com)
  • The expression of miR-138 is activated by GATA1, which in turn is repressed by BCR-ABL. (wikipedia.org)
  • cellular
  • A critical feature of this view is that mRNAs are variably dependent on cellular ribosome concentration, with more poorly initiated mRNAs being typically more sensitive to perturbations in ribosome concentration or function. (sciencemag.org)
  • Consistent with the in vivo observations, knockdown of SLC39A8 in HUVECs decreased ADAMTS1 transcription by decreasing cellular Zn uptake, and as a result, MTF1 transcriptional activity. (jci.org)
  • The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. (wikipedia.org)
  • miRNA
  • Therefore, miR-138, by virtue of a BCR-ABL/GATA1/miR-138 circuitry, is a tumor suppressor miRNA implicated in the pathogenesis of CML and its clinical response to imatinib. (wikipedia.org)
  • binding sites
  • Analysis of the genome‐wide binding properties of TAL1 in these two haematopoietic lineages revealed new insight into the mechanism by which transcription factors select their binding sites in alternate lineages. (embopress.org)
  • promoter
  • The AGGF1 gene promoter does not contain a TATA box and contains 2 transcription start sites that are -367 and -364 base pairs ahead of the base translation start site. (wikipedia.org)
  • tissue
  • Conversely, Tie2 activation normalized pro-thrombotic responses by inhibiting endothelial tissue factor and phosphatidylserine exposure. (jci.org)
  • At the tissue level, Siglec-8 mRNA was found to be most highly expressed in lung, PBMCs, spleen, and kidney. (wikipedia.org)
  • repression
  • Insulin resistance and type 2 diabetes are associated with low levels of high-density lipoprotein cholesterol (HDL-C). The insulin-repressible FoxO transcription factors are potential mediators of the effect of insulin on HDL-C. FoxOs mediate a substantial portion of insulin-regulated transcription, and poor FoxO repression is thought to contribute to the excessive glucose production in diabetes. (jci.org)
  • levels
  • Insulin resistance and type 2 diabetes are associated with low levels of high-density lipoprotein cholesterol (HDL-C). The insulin-repressible FoxO transcription factors are potential mediators of. (jci.org)
  • specific
  • One hypothesis is that ribosome dysfunction (or deficiency) can affect global and messenger RNA (mRNA)-specific translational control, and that certain specific cells or tissues may be more vulnerable to ribosome dysfunction. (sciencemag.org)
  • The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number of T-cell acute lymphoblastic leukemia-specific translocations occur. (wikipedia.org)
  • shown
  • HIF-1a Hypoxia-inducible factor-1alpha (HIF-1a), one of the key regulators in cancer cells, has been shown to be one target of miR-138. (wikipedia.org)
  • control
  • Specifically, murine ES cells were engineered to conditionally suppress Gata1 in the presence of doxycycline (dox), as the result of a Gata1 -targeting shRNA under the control of a tetracycline response element. (jci.org)