HBx natural variants containing Ser-101 instead of Pro-101 evade ubiquitin-dependent proteasomal degradation by activating proteasomal activator 28 gamma expression

Proteasomal activator 28 gamma (PA28γ) is frequently overexpressed in hepatocellular carcinoma; however, its underlying mechanism and role in hepatitis B virus (HBV) replication are largely unknown. Here, we found that HBV X protein (HBx) natural variants containing Ser-101 instead of Pro-101 increase reactive oxygen species levels in the mitochondria and activate the ataxia telangiectasia mutated/checkpoint kinase 2 pathway in the nucleus,...