Caption N-terminal domain A/B domain: ligand-independent domain AF1: Activation Function 1 DBD: DNA Binding Domain LBD: Ligand Binding Domain: ligand-dependent domain AF2: Activation Function 2 C-terminal domain Sumoylation Phosphorylation Structural Organization of PPARγ

Structural Organization of PPARγ-1 and PPARγ-2 PPARγ-1 PPARγ-2 PPARγ-1 and PPARγ-2 are isoforms of PPARγ. PPARγ and PPARγ-1 are structurally identical, though PPARγ-2 has a longer N-terminal domain (30-residue extension of amino acids).

The phosphorylation of PPARγ-2 takes place on S112 (serine 112 site) on the AF1 region. The phosphorylation activates the receptor and results in the adipogenic gene program. Phosphorylation of S112 together with sumoylation of K107 of PPARγ-2 occurs on the AF1 region. This array inhibits the activity of the receptor and results in a reduced adipogenic gene program. The sumoylation of K107 of PPARγ-2 occurs on the AF2 region. It is important for ligand-dependent repression of the inflammatory gene program. a) Phosphorylation of PPARγ-2 b) Phosphorylation and Sumoylation of PPARγ-2 c) Sumoylation of PPARγ-2

c) Ubiquitination of PPARγ-2 K107 sumoylation is to some extent linked to S112 phosphorylation. Sumoylation of transcriptional regulators mostly correlates with the inhibition of transcription. It is assumed that phosphorylation can indicate inhibition or stimulation of transcriptional activity, depending on the cellular background and kinases involved. Ubi