EBNA3C interacts with Gadd34 and counteracts the unfolded protein response.docVIP

Virology Journal BioMedCentral Research Open Access EBNA3C interacts with Gadd34 and counteracts the unfolded protein response Jose L Garrido*1, Seijii Maruo2, Kenzo Takada2 and Adam Rosendorff1 Address: 1University of Pittsburgh and Childrens Hospital of Pittsburgh, One Childrens Hospital Drive, 4401 Penn Ave, Pittsburgh, PA 15224, USA and 2Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-0815, Japan Email: Jose L Garrido* - jlg114@; Seijii Maruo - smaruo@igm.hokudai.ac.jp; Kenzo Takada - kentaka@igm.hokudai.ac.jp; Adam Rosendorff - adam.rosendorff@ * Corresponding author Published: 29 December 2009 Received: 26 October 2009 Accepted: 29 December 2009 Virology Journal 2009, 6:231 doi:10.1186/1743-422X-6-231 This article is available from: /content/6/1/231 ? 2009 Garrido et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract EBNA3C is an EBV-encoded nuclear protein, essential for proliferation of EBV infected B- lymphocytes. Using EBNA3C amino acids 365-545 in a yeast two hybrid screen, we found an interaction with the Growth Arrest and DNA-damage protein, Gadd34. When both proteins are overexpressed, Gadd34 can interact with EBNA3C in both nuclear and cytoplasmic compartments. Amino acids 483-610 of Gadd34, including the two PP1a interaction, and the HSV-1 ICPγ34.5 homology domains, are required for the interaction. Furthermore, interaction is lost with a mutant of EBNA3C (509 DVIEVID 515→AVIAVIA), that abolishes EBNA3C coactivation ability as well as SUMO interaction[1]. In B-cells, Gadd34, and EBNA3C are present in a complex with PP1a using microcystin sepharose affinity purification, Using a lymphob