Therefore, the aims of this study were to i) identify the site of acute tubule injury upon Cul3 deletion and to characterize the time-course of its transition into CKD, thus, establishing KS-Cul3−/− mice as a novel genetic CKD model; ii) test the hypothesis that dysregulation of the cell cycle and Keap1/Nrf2 pathway precedes tubule injury, and that the cyclin E inhibitor roscovitine ameliorates kidney injury; iii) test the hypothesis that CUL3 plays a broader role in kidney disease by examining CUL3 expression in mouse models of AKI and CKD, and in fibrotic human samples. This evidence concerns the gene CCNE1 and chronic kidney disease.