SDP1 is a peroxisome-proliferator-activated receptor γ2 co-activator that binds through its SCAN domain

Peroxisome-proliferator-activated receptors (PPARs), members of the nuclear hormone receptor superfamily, play an important role in the regulation of lipid metabolism and energy homoeostasis. In a yeast two-hybrid experiment using the zinc-finger transcription factor ZNF202 as bait, we previously identified the SCAN-domain-containing protein SDP1. SDP1 shares a high degree of amino acid sequence identity with PGC-2, a previously identified PPARgamma2 co-activator from the mouse. Here we show that SDP1 and PGC-2 interact with PPARgamma2 through their SCAN domains, even though PPARgamma2 does not contain a SCAN domain. Similar to PGC-2, SDP1 enhanced PPARgamma2-dependent gene transcription in transiently transfected cells but did not alter the affinity of PPARgamma2 for agonists. Although the SCAN domain was necessary for binding to PPARgamma2 it was not sufficient for co-activation in cells, suggesting that other features of SDP1 are responsible for transcriptional co-activation. The ability of SDP1 to interact with two different transcription factors that regulate genes involved in lipid metabolism, ZNF202 and PPARgamma2, suggests that SDP1 may be an important coregulator of such genes.