Depletion of CSN5 inhibits Ras-mediated tumorigenesis by inducing premature senescence in p53-null cells

► Depletion of CSN5 prevents formation of tumors by Ras transformed cells. ► Depletion of CSN5 suppresses cell proliferation, and induces premature senescence. ► CSN5-depleted cells exhibit enhanced activation of the PI3 kinase-Akt pathway. ► Wortmannin reduces the level of premature senescence. ► CSN5 may be a novel target in cancer therapy against tumors with mutation in p53.