title: Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation.
abstract: Members of the cdc25 family are protein phosphatases that play pivotal roles in cell cycle progression. Cdc25A has been shown to be a critical regulator of the G1/S transition of mammalian cells and to be a myc-target gene with oncongenic properties. We investigated the regulation of cdc25A during terminal differentiation using myeloblastic leukemia M1 cells, that can be induced to undergo differentiation into macrophages by interleukin-6 (IL-6) treatment. In this report it is shown that cdc25A protein is degraded by the ubiquitin-proteasome machinery in both terminally differentiating and cycling 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 obtained that degradation of cdc25A by the ubiquitin-proteasome machinery in terminally differentiating myeloid cells is accelerated compared to cycling cells. Moreover, deregulated expression of c-myc in M1 cells, which had been previously shown to block terminal differentiation, was also found to block IL-6 induced degradation of cdc25A.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N. Broad Street, Philadelphia, Pennsylvania, PA 19140, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bernardi
authors.forename: D A
authors.initials: DA
authors.lastname: Liebermann
authors.forename: B
authors.initials: B
authors.lastname: Hoffman
mesh_terms: D002453:Cell Cycle; D002454:Cell Differentiation; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014452:Ubiquitins; D020687:cdc25 Phosphatases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex