APC/C (Cdh1) controls the proteasome-mediated degradation of E2F3 during cell cycle exit.

Cell Cycle
Zhen PingDaniele Guardavaccaro

Abstract

E2F transcription factors regulate gene expression in concert with the retinoblastoma tumor suppressor family. These transcriptional complexes are master regulators of cell cycle progression and, in addition, control the expression of genes involved in DNA repair, G 2/M checkpoint and differentiation. E2F3 has recently attracted particular attention, because it is amplified in various human tumors. Here we show that E2F3 becomes unstable as cells exit the cell cycle. E2F3 degradation is mediated by the anaphase-promoting complex/cyclosome and its activator Cdh1 (APC/C (Cdh1) ). E2F3 interacts with Cdh1 but not Cdc20, the other APC/C activator. Enforced expression of Cdh1 results in proteasome-dependent degradation of E2F3, whereas the overexpression of Cdc20 has no effect on E2F3 turnover. Finally, silencing of Cdh1 by RNA interference stabilizes E2F3 in differentiating neuroblastoma cells. These findings indicate that the APC/C (Cdh1) ubiquitin ligase targets E2F3 for proteasome-dependent degradation during cell cycle exit and neuronal differentiation.

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Citations

Apr 24, 2014·The Journal of Pathology·Benito CamposChristel Herold-Mende
May 16, 2017·International Journal of Molecular Sciences·Tanja FuchsbergerJose Viña
Sep 10, 2014·Molecular and Cellular Biology·Jihoon KimDaniele Guardavaccaro
Feb 13, 2020·Reproductive Sciences·Guoli ZhouAna Vazquez
Jan 31, 2017·The Journal of Clinical Investigation·Lindsey N KentGustavo Leone
Mar 7, 2020·Scientific Reports·Alanna B ChanKatja A Lamia
Feb 7, 2014·The Journal of Biological Chemistry·Sara D'AnnibaleDaniele Guardavaccaro
Jan 6, 2018·Cancer Biology & Therapy·Yan ZhangChang Liu
Jun 11, 2021·Frontiers in Cell and Developmental Biology·Tatyana BodrugNicholas G Brown

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