PROTEIN KINASE R

'Protein kinase R' ('PKR') is activated by double-stranded RNA (dsRNA) and plays a major role in the cellular response to viral infection. PKR can also be activated by the protein PACT or by heparin. PKR contains an N-terminal dsRNA binding domain (dsRBD) and a C-terminal kinase domain, that gives it pro-apoptotic (cell-killing) functions. The dsRBD consists of two tandem copies of a conserved double stranded RNA binding motif, dsRBM1 and dsRBM2. PKR is induced by interferon in a latent state. Binding to dsRNA is believed to activate PKR by inducing dimerization and subsequent autophosphorylation reactions. In situations of viral infection, the dsRNA created by viral replication and gene expression binds to the N-terminal domain, activating the protein and causing apoptosis of the cell to prevent further viral spread. However, latent infection by certain viruses such as Epstein-Barr Virus (EBV) in conjunction with a viral gene known as EBER-1 can lead to inactivation of PKR, leading to cancers such as Burkitt's Lymphoma, Hodgkin's Disease, Nasopharyngeal carcinoma and various Leukemias.