Skip to main content
. 2013 Oct 25;4:2667. doi: 10.1038/ncomms3667

Figure 10. Differential regulation of the REGγ–20S proteasome pathway by p53/Smad3 and mutant p53 in cancer cells.

Figure 10

A hypothetic model that illustrates (a) both TGF-β and p53 signalling suppress the ubiquitin/ATP-independent REGγ–20Sproteasome pathway via REGγ. Smad3 and p53 proteins negatively regulate REGγ expression through recruitment of its co-repressors. The net output of this mechanism is to prevent the degradation of tumour suppressor proteins and, subsequently, inhibit cancer progression, cell proliferation and decrease drug resistance in cancer cells. (b) Novel GOF of mutant p53: mutant p53 exerts bipartite mechanism to enhance the REGγ–20S proteasome pathway in cancer cells. On one side, mutant p53 binds and recruits p300, a coactivator, and on another side block the recruitment of the Smad3/N-CoR complex formation on REGγ promoter in response to TGF-β. The net gain of this mechanism is to enhance the REGγ–20S proteasome pathway via REGγ in cancer cells to accelerate cancer progression, promote cell proliferation and increase drug resistance during tumour development.