ORCID Profile
0000-0003-4186-684X
Current Organisations
Agency for Science, Technology and Research
,
Nanyang Technological University
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Publisher: Oxford University Press (OUP)
Date: 23-05-2014
DOI: 10.1093/NAR/GKU430
Publisher: Oxford University Press (OUP)
Date: 26-07-2011
DOI: 10.1002/STEM.666
Abstract: Activin/Nodal signaling is necessary to maintain pluripotency of human embryonic stem cells (hESCs) and to induce their differentiation toward endoderm. However, the mechanisms by which Activin/Nodal signaling achieves these opposite functions remain unclear. To unravel these mechanisms, we examined the transcriptional network controlled in hESCs by Smad2 and Smad3, which represent the direct effectors of Activin/Nodal signaling. These analyses reveal that Smad2/3 participate in the control of the core transcriptional network characterizing pluripotency, which includes Oct-4, Nanog, FoxD3, Dppa4, Tert, Myc, and UTF1. In addition, similar experiments performed on endoderm cells confirm that a broad part of the transcriptional network directing differentiation is downstream of Smad2/3. Therefore, Activin/Nodal signaling appears to control ergent transcriptional networks in hESCs and in endoderm. Importantly, we observed an overlap between the transcriptional network downstream of Nanog and Smad2/3 in hESCs whereas, functional studies showed that both factors cooperate to control the expression of pluripotency genes. Therefore, the effect of Activin/Nodal signaling on pluripotency and differentiation could be dictated by tissue specific Smad2/3 partners such as Nanog, explaining the mechanisms by which signaling pathways can orchestrate ergent cell fate decisions.
Publisher: Public Library of Science (PLoS)
Date: 22-01-2016
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.CCR.2010.04.028
Abstract: Overexpression of phosphatase of regenerating liver (PRL)-3 is associated with the progression of erse human cancers. We show that the overexpression of PRL-3 protein is not directly associated with its transcript levels, indicating the existence of an underlying posttranscriptional regulation. The 5' untranslanted region (UTR) of PRL-3 mRNA possesses triple GCCCAG motifs capable of suppressing mRNA translation through interaction with PolyC-RNA-binding protein 1 (PCBP1), which retards PRL-3 mRNA transcript incorporation into polyribosomes. Overexpression of PCBP1 inhibits PRL-3 expression and inactivates AKT, whereas knockdown of PCBP1 causes upregulation of PRL-3 protein levels, activation of AKT, and promotion of tumorigenesis. An inverse correlation between protein levels of PRL-3 and PCBP1 in human primary cancers supports the clinical relevance.
Publisher: Informa UK Limited
Date: 20-12-2014
DOI: 10.4161/RNA.27427
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Leah Vardy.