Monday, April 07, 2008

Essential role of PKCd in HDACi-induced EBV reactivation in NPC cells

Essential role of PKC{delta} in histone deacetylase inhibitor-induced Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells
Lee HH, Chang SS, Lin SJ, Chua HH, Tsai TJ, Tsai K, Lo YC, Chen HC, Tsai CH.
J Gen Virol.2008; 89: 878-883

Although this has been on the web for several weeks, I don't know why I didn't post this back then. Maybe I was overjoyed or something... Anyway, for all my friends who are curious what my previous research project is, here it is.

Condensing it in my own words:
We found that PKC-delta specific inhibitors (in the form of a drug called Rottlerin) were able to block the EBV reactivation by histone deacetylase inhibitor (HDACi) drugs. Thus we set out to test if PKC-delta is essential to EBV reactivation, and if yes, what role does it play. If PKC-delta is activated, then it would be phosphorylated on the activation site and translocate to the cell nucleus. By doing immuno-florescence microscopy, we have found that PKC-delta showed up as speckles in the cell nucleus about 8 hours after the drug induction of EBV reactivation. This was also supported by testing the phosphorylation of PKC-delta, thus supporting the view that PKC-delta plays a role in the pathway that leads to EBV reactivation. Also, by doing reporter assays, we can show that an over expression of PKC-delta alone could promote EBV reactivation, showing that PKC-delta is sufficient to reactivate EBV replication. I am fascinated by viral reactivation from latency to the lytic cycle, and this study opens a new pathway that has yet been found in EBV (though previously found in KSHV), and as we don't know at this stage what is up stream or down stream of PKC-delta, I think this is an interesting topic to work on, either to learn more about the regulation of viral replication, or how it responds to changes in the cell.

Well, that's about the story that I told during most of my grad school interviews. Pretty neat that through out the interviews, telling the story and discussing it with various faculty at different schools, I gradually get a better and better feel of my own project; and ironically, much more so then I ever did while working on it... And thus, sometimes it feels very exciting to talk to faculty that digs into the details of my project and discuss possible points of farther exploration. In a sense, sometimes it's good to be grilled during interviews as long as you know your project and they grill you in a reasonable way. (The uncomfortable "grillings" goes like "why's your GRE score so low...?")

Cool stuff ^^

Oh, I might be working on the epigenetics of viral gene regulations in the future. As I don't think this is a good place to discuss a "in-the-works" research project, I think my next time discussing it here would be when the next paper on my future project comes out, hope that would be soon.

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