PPAR and Agonists against Cancer: Rational Design of Complementation Treatments
Figure 2
Mechanisms of
transrepression by PPARγ. (a) Ligand-independent
repression: preferential recruitment of corepressors in the absence of
agonists. (b) Direct binding and sequestration of transcription factors
on example of NFκB. (c) Activation of genes
encoding inhibitors of transcription factor (e.g., NFκB inhibitor, IκBα). (d) Direct binding and
inactivation of kinases, which activate transcription factors (e.g., the
blockade of JNK activation of cJun). (e) Competitive binding of the
coactivator complex. (f) The blockade of corepressor clearance:
sumoylated PPARγ stabilizes corepressor complexes (NCoR,
Tab2, and TBL1) on the promoter and facilitates the recruitment of HDAC3. In
the absence of sumoylation, NCoR, Tab2, and TBL1 are subject to ubiquitination
and proteasomal clearance.
