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 PPARγ2 co-activator from the mouse. Here we show that SDP1 and PGC-2 interact with PPARγ2 through their SCAN domains, even though PPARγ2 does not contain a SCAN domain. Similar to PGC-2, SDP1 enhanced PPARγ2-dependent gene transcription in transiently transfected cells but did not alter the affinity of PPARγ2 for agonists. Although the SCAN domain was necessary for binding to PPARγ2, 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 PPARγ2, suggests that SDP1 may be an important co-regulator of such genes.
- peroxisome-proliferator-activated receptor
- zinc finger
↵1 Present address: Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, U.S.A.
Abbreviations used: AF-1, activation function-1; DBD, DNA-binding domain; DMEM, Dulbecco's modified Eagle's medium; ER, oestrogen receptor; FBS, fetal bovine serum; GST, glutathione S-transferase; LBD, ligand-binding domain; LPL, lipoprotein lipase; NHR, nuclear hormone receptor; PGC-2, PPARγ co-activator-2; PPAR, peroxisome-proliferator-activated receptor; PPRE, PPAR response element; RXR, retinoic acid receptor; SDP1, SCAN-domain-containing protein 1; SRC-1, steroid receptor co-activator-1.
- The Biochemical Society, London ©2003