2,265 research outputs found
Association of pancreatic autoantibodies and human leukocyte antigen haplotypes with resolution of diabetes mellitus following therapy for hepatitis C virus infection in patients with human immunodeficiency virus infection
No full textPurification and biochemical characteristics of occlusion body of Penaeus-monodon-type baculovirus (MBV).
No full textExperimental infection of white spot baculovirus in some cultured and wild decapods in Taiwan.
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Identification of white spot syndrome associated baculovirus (WSBV) target organs in the shrimp Penaeus monodon by in situ hybridization.
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Upregulation of Id1 by Epstein-Barr Virus-encoded LMP1 confers resistance to TGFβ-mediated growth inhibition
Get PDFBackground
Epstein-Barr virus (EBV)-encoded LMP1 protein is commonly expressed in nasopharyngeal carcinoma (NPC). LMP1 is a prime candidate for driving tumourigenesis given its ability to activate multiple signalling pathways and to alter the expression and activity of variety of downstream targets. Resistance to TGFβ-mediated cytostasis is one of the growth transforming effects of LMP1. Of the downstream targets manipulated by LMP1, the induction of Id1 and inactivation of Foxo3a appear particularly relevant to LMP1-mediated effects. Id1, a HLH protein is implicated in cell transformation and plays a role in cell proliferation, whilst Foxo3a, a transcription factor controls cell integrity and homeostasis by regulating apoptosis. The mechanism(s) by which LMP1 induces these effects have not been fully characterised.
Results
In this study, we demonstrate that the ability of LMP1 to induce the phosphorylation and inactivation of Foxo3a is linked to the upregulation of Id1. Furthermore, we show that the induction of Id1 is essential for the transforming function of LMP1 as over-expression of Id1 increases cell proliferation, attenuates TGFβ-SMAD-mediated transcription and renders cells refractory to TGFβ-mediated cytostasis. Id1 silencing in LMP1-expressing epithelial cells abolishes the inhibitory effect of LMP1 on TGFβ-mediated cell growth arrest and reduces the ability of LMP1 to attenuate SMAD transcriptional activity. In response to TGFβ stimulation, LMP1 does not abolish SMAD phosphorylation but inhibits p21 protein expression. In addition, we found the induction of Id1 in LMP1-expressing cells upon stimulation by TGFβ. We provide evidence that LMP1 suppresses the transcriptional repressor ATF3, possibly leading to the TGFβ-induced Id1 upregulation.
Conclusion
The current data provide novel information regarding the mechanisms by which LMP1 suppresses TGFβ-induced cytostasis, highlighting the importance of Id1 in LMP1 mediated cell transformation
Programmable Cellular Retention of Nanoparticles by Replacing the Synergistic Anion of Transferrin
No full text[[abstract]]The ability to program the intracellular retention of nanoparticles (NPs) would increase their applicability for imaging and therapeutic applications. To date, there has been no efficient method developed to control the fate of NPs once they enter cells. Existing approaches to manipulate the intracellular retention of NPs are mostly "passive" and particle size-dependent. Different sized particles hold distinct cellular responses. The adverse effect of particle size may limit the utility of nanodelivery systems. Therefore, the development of tunable/"active" NP intracellular retention systems with fixed particle sizes remains a considerable challenge. By replacing the synergistic anions of transferrin (If) immobilized on quantum dots (Tf-QDs, ca. 25 nm), we have examined the feasibility of this concept. Substitution of synergistic anions of If from carbonate (holo-Tf) to oxalate (oxa-Tf) significantly increased the intracellular accumulation of the oxa-Tf-QDs as a result of (I) a delay In cellular removal triggered by oxalate (oxa-Tf)-Induced endosomal If iron-release retardation and (ii) enhanced recycling of Tf-QD/TfR (Tf receptor) complexes from early endosomes to the plasma membrane. This accumulation extended the intracellular NP retention interval. The half-maximum fluorescence intensity of the oxa-Tf-QDs in vivo was 4 times higher than that of the holo-Tf-QDs. Programming of the intracellular NP retention time was accomplished through manipulation of the ratio of holo- and oxa-Tfs on the surfaces of the QDs. Using this simple and efficient approach, it was possible to readily achieve a desirable Intracellular retention Interval for the NPs.[[note]]SC
A vaccine-associated rhabdomyosarcoma with spinal epidural invasion and pulmonary metastases in a cat
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