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EBV Conference 2008 Guangzhou - Baylor College of Medicine

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64 (RegID: 1259)<br />

Daniel Portal<br />

Institution: Brigham and Women's Hospital, Harvard University<br />

e-mail: dportal@rics.bwh.harvard.edu<br />

EBNA-LP RELOCALIZES SMRT/NCOR AND HDAC5 FROM MAD BODIES TO THE<br />

NUCLEOPLASM<br />

DANIEL PORTAL AND ELLIOTT KIEFF<br />

Posterabstract:<br />

Epstein-Barr nuclear antigen (EBNA) leader protein (EBNA-LP) coactivates promoters with EBNA2 and<br />

is important for Epstein-Barr virus immortalization <strong>of</strong> B cells. EBNA2 activates transcription by<br />

associating with RBP/CSL and displacing SMRT/NCoR-HDAC5 corepressor complex. We investigated<br />

EBNA-LP’s role in coactivation with EBNA2 by affecting SMRT/NCoR-HDAC5 from their subnuclear<br />

localization. At steady state, SMRT/NCoR-HDAC5 localize to Matrix-Associated Deacetylase (MAD)<br />

Bodies as well as diffusely in the nucleus and cytoplasm. EBNA-LP’s presence completely relocalizes<br />

SMRT/NCoR and HDAC5 from MAD bodies to a diffuse nuclear distribution. Moreover, SMRT/NCoR<br />

and HDAC5’s diffuse distribution completely colocalizes with EBNA-LP’s distribution, but not with<br />

active transcription as determined by H3K4 co-immunostaining, suggesting that EBNA-LP is not present<br />

at sites <strong>of</strong> active transcription. MAD bodies’ disruption appears to be dependent on EBNA-LP’s ability to<br />

interact with HA95, a nuclear matrix protein, since an EBNA-LP protein unable to associate with HA95 is<br />

10 fold less efficient at relocating SMRT/NCoR and HDAC5.These data further strengthen EBNA-LP’s<br />

role in coactivation <strong>of</strong> transcription by relocating repressors from their steady state subcellular<br />

localization.<br />

<strong>EBV</strong> <strong>Conference</strong> <strong>2008</strong> <strong>Guangzhou</strong><br />

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