Biting the hand that feeds: Rpn4-dependent feedback regulation of proteasome function.

The 26S proteasome of eukaryotic cells mediates ubiquitin-dependent as well as ubiquitin-independent degradation of proteins in many regulatory processes as well as in protein quality control. The proteasome itself is a dynamic complex with varying compositions and interaction partners. Studies in Saccharomyces cerevisiae have revealed that expression of proteasome subunit genes is coordinately controlled by the Rpn4 transcriptional activator. The cellular level of Rpn4 itself is subject to a complex regulation, which, aside of a transcriptional control of its gene, intriguingly involves ubiquitin-dependent as well as ubiquitin-independent control of its stability by the proteasome. A novel study by Ju et al. [D. Ju, H. Yu, X. Wang, Y. Xie, Ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation-dependent ubiquitylation signal, Biochim. Biophys. Acta (in press), doi:10.1016/j.bbamcr.2007.04.012] now revealed another level of complexity by showing that phosphorylation of a specific serine residue in Rpn4 is required for its efficient targeting by the Ubr2 ubiquitin ligase.