Evolutionarily Conserved Roles for Apontic in Induction and Subsequent Decline of Cyclin E Expression

Summary Cyclin E is a key factor for S phase entry, and deregulation of Cyclin E results in developmental defects and tumors. Therefore, proper cycling of Cyclin E is crucial for normal growth. Here we found that transcription factors Apontic (Apt) and E2f1 cooperate to induce cyclin E in Drosophila. Functional binding motifs of Apt and E2f1 are clustered in the first intron of Drosophila cyclin E and directly contribute to the cyclin E transcription. Knockout of apt and e2f1 together abolished Cyclin E expression. Furthermore, Apt up-regulates Retinoblastoma family protein 1 (Rbf1) for proper chromatin compaction, which is known to repress cyclin E. Notably, Apt-dependent up-regulation of Cyclin E and Rbf1 is evolutionarily conserved in mammalian cells. Our findings reveal a unique mechanism underlying the induction and subsequent decline of Cyclin E expression.
Graphical Abstract
Highlights • Mutual activation of apt and e2f1 promotes rapid induction of CycE at S phase entry • Apt also up-regulates Rbf1, but Rbf1 is inactivated through phosphorylation by Cdk2 • After initiation of S phase, Rbf1 becomes active and represses cycE • Apt governs both induction and subsequent repression of cycE
Biological Sciences; Molecular Biology; Cell Biology