Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation

Members of the cdc25 family are protein phosphatases that play pivotal role s in cell cycle progression. Cdc25A has been shown to be a critical regulat or of the G1/S transition of mammalian cells and to be a myc-target gene wi th oncongenic properties. We investigated the regulation of cdc25A during t erminal differentiation using myeloblastic leukemia M1 cells, that can be i nduced to undergo differentiation into macrophages by interleukin-6 (IL-6) treatment. In this report it is shown that cdc25A protein is degraded by th e ubiquitin-proteasome machinery in both terminally differentiating and cyc ling cells. Cdc25A was found to have two major peaks of accumulation during cell cycle progression, one in G1 and the other in S/G2, Evidence was obta ined that degradation of cdc25A by the ubiquitin-proteasome machinery in te rminally differentiating myeloid cells is accelerated compared to cycling c ells, Moreover, deregulated expression of c-myc in M1 cells, which had been previously shown to block terminal differentiation, was also found to bloc k IL-6 induced degradation of cdc25A.