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 identify molecular targets and regulatory partners of TLS. Here we report that TLS regulates the expression of oxidative stress protection genes. This regulation requires interaction with the transcriptional coactivator peroxisome proliferator activated receptor g-coactivator 1a (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-1a, and is thus largely dependent on PGC-1a. 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.

Resumen del póster presentado al International Symposium on Redox Signaling and Oxidative Stress in Health and Disease, IV Spanish and Portuguese Meeting on Free Radicals; celebrado en Valencia (España) del 5 al 7 de junio de 2012.-- et al.

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