Fig. 3. A model for -arrestin-mediated regulation of transcription. (a) Direct pathway. In response to receptor activation, -arrestins translocate from the cytoplasm to the nucleus and associate with transcription cofactors such as p300 and CREB at the promoters of target genes to promote transcription directly. (b) Indirect pathway. -arrestins interact with regulators of transcription factors such as IB and MDM2 in the cytoplasm, which results in changes in activity and the subcellular distribution of these binding partners, and thus exert regulatory effects on the activation of transcription factors indirectly. Ub, ubiquitylation.