Everett, R.D., Meredith, M., Orr, A., Cross, A., Kathoria, M., and Parkinson, J. (1997) A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO Journal, 16(7). pp. 1519-1530. (doi:10.1093/emboj/16.7.1519)
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Herpes simplex virus type 1 immediate-early protein Vmw110 is a non-specific activator of gene expression and is required for efficient initiation of the viral lytic cycle. Since Vmw110-deficient viruses reactivate inefficiently in mouse latency models it has been suggested that Vmw110 plays a role in the balance between the latent and lytic states of the virus. The mechanisms by which Vmw110 achieves these functions are poorly understood. Vmw110 migrates to discrete nuclear structures (ND10) which contain the cellular PML protein, and in consequence PML and other constituent proteins are dispersed. In addition, Vmw110 binds to a cellular protein of approx135 kDa, and its interactions with the 135 kDa protein and ND10 contribute to its ability to stimulate gene expression and viral lytic growth. In this report we identify the 135 kDa protein as a novel member of the ubiquitin-specific protease family. The protease is distributed in the nucleus in a micropunctate pattern with a limited number of larger discrete foci, some of which co-localize with PML in ND10. At early times of virus infection, the presence of Vmw110 increases the proportion of ND10 which contain the ubiquitin-specific protease. These results identify a novel, transitory component of ND10 and implicate a previously uncharacterized ubiquitin-dependent pathway in the control of viral gene expression.
|Glasgow Author(s) Enlighten ID:||Everett, Professor Roger and Orr, Mrs Anne|
|Authors:||Everett, R.D., Meredith, M., Orr, A., Cross, A., Kathoria, M., and Parkinson, J.|
|College/School:||College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation|
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
|Journal Name:||EMBO Journal|