Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Centre de Recherche en Cancerologie de Lyon, 28 rue Laennec, 69008, Lyon, France.
Sci Rep. 2020 Mar 5;10(1):4077. doi: 10.1038/s41598-020-61087-y.
Early 2 factor (E2F) family transcription factors participate in myriad cell biological processes including: the cell cycle, DNA repair, apoptosis, development, differentiation, and metabolism. Circadian rhythms influence many of these phenomena. Here we find that a mammalian circadian rhythm component, Cryptochrome 2 (CRY2), regulates E2F family members. Furthermore, CRY1 and CRY2 cooperate with the E3 ligase complex SKP-CULLIN-FBXL3 (SCF) to reduce E2F steady state protein levels. These findings reveal an unrecognized molecular connection between circadian clocks and cell cycle regulation and highlight another mechanism to maintain appropriate E2F protein levels for proper cell growth.
早期 2 因子 (E2F) 家族转录因子参与众多细胞生物学过程，包括：细胞周期、DNA 修复、细胞凋亡、发育、分化和代谢。昼夜节律会影响其中许多现象。在这里，我们发现哺乳动物昼夜节律成分 Cryptochrome 2 (CRY2) 可以调节 E2F 家族成员。此外，CRY1 和 CRY2 与 E3 连接酶复合物 SKP-CULLIN-FBXL3 (SCF) 合作，降低 E2F 稳定状态蛋白水平。这些发现揭示了昼夜节律钟和细胞周期调控之间的一个未被识别的分子联系，并强调了另一种机制来维持适当的 E2F 蛋白水平，以实现细胞的正常生长。
