Feedback regulation between atypical E2Fs and APC/C-Cdh1 coordinates cell cycle progressionBoekhout, M., Yuan, R., Wondergem, A. P., Segeren, H. A., van Liere, E. A., Awol, N., Jansen, I., Wolthuis, R. M. F., de Bruin, A. & Westendorp, B., Mar-2016, In : Embo Reports. 17, 3, p. 414-427 14 p.
Research output: Contribution to journal › Article › Academic › peer-review
E2F transcription factors control the oscillating expression pattern of multiple target genes during the cell cycle. Activator E2Fs, E2F1-3, induce an upswing of E2F targets, which is essential for the G1-to-S phase transition, whereas atypical E2Fs, E2F7 and E2F8, mediate a downswing of the same targets during late S, G2, and M phases. Expression of atypical E2Fs is induced by E2F1-3, but it is unknown how atypical E2Fs are inactivated in a timely manner. Here, we demonstrate that E2F7 and E2F8 are substrates of the anaphase-promoting complex/cyclosome (APC/C). Removal of CDH1, or mutating the CDH1-interacting KEN boxes, stabilized E2F7/8 from anaphase onwards and during G1. Expressing KEN mutant E2F7 during G1 impairs S phase entry and eventually results in cell death. Furthermore, we show that E2F8, but not E2F7, interacts also with APC/C-Cdc20. Importantly, atypical E2Fs can activate APC/C-Cdh1 by repressing its inhibitors cyclin A, cyclin E, and Emi1. In conclusion, we discovered a feedback loop between atypical E2Fs and APC/C-Cdh1, which ensures balanced expression of cell cycle genes and normal cell cycle progression.
|Number of pages||14|
|Publication status||Published - Mar-2016|
- anaphase-promoting complex, CDH1, cell cycle, DNA replication, E2F, UBIQUITIN CHAIN FORMATION, DNA-DAMAGE, S-PHASE, REPLICATION STRESS, MEDIATED DEGRADATION, ANAPHASE, CANCER, TRANSCRIPTION, GENES