Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles.
Megakaryocytes become polyploid by entering a truncated cell cycle, consisting of alternate S phases and abortive mitoses. We have investigated the regulation of the G1/S transition by comparing two megakaryoblastic cell lines, HEL and K562, which respectively do or do not become polyploid in response to phorbol esters. A pronounced downregulation of cyclin A, and to a lesser extent of cyclin E, occurred in K562 cells during the first 24 h after TPA treatment, in contrast with re-replicating HEL cells, in which both cyclins were present in individual G2/M cells. Transactivation experiments suggested that the absence of cyclin A in differentiated K562 cells could be due to a TPA-mediated inhibition of its transcription. To investigate the potential role of cyclin E in the establishment of re-replication cycles, we isolated K562 clones constitutively expressing cyclin E. The resulting clones, and also K562 cells transiently expressing cyclin E, entered re-replication cycles when treated with TPA. The transcriptional activity of the cyclin A promoter was not inhibited after TPA treatment, and although the levels of cyclin A fluctuated during further re-replication cycles, they never decreased below S phase levels. We conclude that the presence of cyclin E in megakaryoblastic G2/M cells determines cyclin A expression and allows the entrance into an extra S phase.
García
P
P
Departamento de Bioquímica, Instituto de Investigaciones Biomédicas A. Sols, Universidad Autónoma-CSIC, Madrid, Spain.
Frampton
J
J
Ballester
A
A
Calés
C
C
D001854:Bone Marrow Cells / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000096:biosynthesis; D019927:Cyclin E / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D016195:G2 Phase; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008938:Mitosis; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D016196:S Phase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases / Q000096:biosynthesis
D018797:Cell Cycle Proteins; D019925:Cyclin A; D019926:Cyclin B; D019927:Cyclin E; D008869:Microtubule-Associated Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D013755:Tetradecanoylphorbol Acetate