Caspase-dependent cleavage regulates protein levels of Epstein-Barr virus-derived latent membrane protein 1

Abstract

Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) plays pathogenic roles in EBV-related diseases. Thus, host cells employ several mechanisms to regulate LMP1 functions, and we previously reported possible regulation by signal transducing adaptor protein-2 as well as BS69. Here, we found that caspase-3 mainly degraded LMP1 proteins in HeLa cells, leading to decreased NF-κB and STAT3 activation. Caspase-3 cleaved the consensus DNTD sequences in the CTAR3 region of LMP1. Of importance, LMP1 expression strongly enhanced caspase-3 activity. Taken together, the reduction of LMP1 protein levels by caspases is likely to be a newly identified host defense against EBV infection.