Exposure of various human cell lines to ultraviolet (UV) light leads to rapid decline in CDC25A but not CDC25B or CDC25C protein levels in a 26S proteasome-dependent manner, with no change in CDC25A mRNA level and preceded by the appearance of polyubiquitinated CDC25A (PolyUb-CDC25A) (Mailand et al. 2000). CDC25A protein and its phosphatase activity decline within 30 minutes of UV exposure (Mailand et al. 2000). CDC25A is required for removal of inhibitory phosphorylation p-Y15 from CDK2 during G1/S transition and the degradation of CDC25A leads to persistent inhibitory phosphorylation of CDK2 (Mailand et al. 2000).
As many nuclear proteins are degraded by the nuclear proteasomes and as the amount of nuclear proteasomes increases as the cell cycle progresses, supposedly for rapid degradation of cell cycle regulators (Bader et al. 2007, Kito et al. 2020), proteasomal degradation of CDC25A is shown to occur in the nucleus.
Xiao, Z, Chen, Z, Gunasekera, AH, Sowin, TJ, Rosenberg, SH, Fesik, S, Zhang, H
Busino, L, Donzelli, M, Chiesa, M, Guardavaccaro, D, Ganoth, D, Dorrello, NV, Hershko, A, Pagano, M, Draetta, GF
Piao, S, Lee, SJ, Xu, Y, Gwak, J, Oh, S, Park, BJ, Ha, NC
Mailand, N, Lukas, C, Syljuâsen, RG, Welcker, M, Lukas, J
endopeptidase activity of 26S proteasome [nucleoplasm]
© 2026 Reactome
