| 1. |
|
|
| 2. |
|
|
| 3. |
- Bergqvist, Anders, et al.
(författare)
-
The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+ Oscillations
- 2003
-
Ingår i: Journal of Biological Chemistry. - : ASBMB. - 0021-9258 .- 1083-351X. ; 278:21, s. 18877-18883
-
Tidskriftsartikel (refereegranskat)abstract
- Alterations of cytokine responses are thought to favor the establishment of persistent hepatitis C virus (HCV) infection, enhancing the risk of liver cirrhosis and hepatocellular carcinoma. Expression of the HCV core (C) protein modulates transcription of the IL-2 promoter in T lymphocytes by activating the nuclear factor of activated T lymphocyte (NFAT) pathway. Here we report on the effect of HCV C on Ca2+ signaling, which is essential for activation of NFAT. Expression of HCV C correlated with increased levels of cytosolic Ca2+ and spontaneous Ca2+ oscillations in transfected Jurkat cells. Triggering of the T-cell receptor induced a prolonged Ca2+ response characterized by vigorous high frequent oscillations in a high proportion of the responding cells. This was associated with decreased sizes and accelerated emptying of the intracellular calcium stores. The effect of HCV C on calcium mobilization was not dependent on phospholipase C-1 (PLC-) activity or increased inositol 1,4,5-trisphosphate (IP3) production and did not require functional IP3 receptors, suggesting that insertion of the viral protein in the endoplasmic reticulum membrane may be sufficient to promote Ca2+ leakage with dramatic downstream consequences on the magnitude and duration of the response. Our data suggest that expression of HCV C in infected T lymphocytes may contribute to the establishment of persistent infections by inducing Ca2+ oscillations that regulate both the efficacy and information content of Ca2+ signals and are ultimately responsible for induction of gene expression and functional differentiation.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Heessen, S, et al.
(författare)
-
Functional p53 chimeras containing the Epstein-Barr virus Gly-Ala repeat are protected from Mdm2- and HPV-E6-induced proteolysis
- 2002
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99:3, s. 1532-1537
-
Tidskriftsartikel (refereegranskat)abstract
- Functional inactivation of the tumor suppressor protein p53 by accelerated ubiquitin/proteasome-dependent proteolysis is a common event in tumor progression. Proteasomal degradation is inhibited by the Gly-Ala repeat (GAr) of the Epstein–Barr virus nuclear antigen-1, which acts as a transferable element on a variety of proteasomal substrates. We demonstrate that p53 chimeras containing GAr domains of different lengths and positions within the protein are protected from proteolysis induced by the ubiquitin ligases murine double minute 2 and E6-associated protein but are still ubiquitinated and retain the capacity to interact with the S5a ubiquitin-binding subunit of the proteasome. The GAr chimeras transactivate p53 target genes, induce cell cycle arrest and apoptosis, and exhibit improved growth inhibitory activity in tumor cells with impaired endogenous p53 activity.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
