PGC-1α Regulates Translocated in Liposarcoma Activity: Role in Oxidative Stress Gene Expression

Abstract

Translocated in liposarcoma (TLS) is a poorly characterized multifunctional protein involved in the genotoxic response. TLS regulates gene expression at several steps, including splicing and mRNA transport, possibly connecting transcriptional and posttranscriptional events. In this study we aimed to idenfity molecular targets and regulatory partners of TLS. Here we report that TLS transcriptionally regulates the expression of oxidative stress protection genes. This regulation requires interaction with the transcriptional coactivator peroxisome proliferator activated receptor γ-coactivator 1α (PGC-1α), a master regulator of mitochondrial function that coordinately induces the expression of genes involved in detoxification of mitochondrial reactive oxygen species (ROS). Microarray gene expression analysis showed that TLS transcriptional activity is impaired in the absence of PGC-1α, and is thus largely dependent on PGC-1α. These results suggest the existence of a regulatory circuit linking the control of ROS detoxification to the coordinated cross-talk between oxidative metabolism and the cellular response to genomic DNA damage.