Activating transcription factor 2 (ATF2) and its homolog ATF7 are phosphorylated at Thr-69/Thr-71 and at Thr-51/Thr-53, respectively, by stress-activated MAPKs regulating their transcriptional functions in G1 and S phases. However, little is known about the role of ATF2 and ATF7 in G2/M phase. Here, we show that Cdk1-cyclin B1 phosphorylates ATF2 at Thr-69/Thr-71 and ATF7 at Thr-51/Thr-53 from early prophase to anaphase in the absence of any stress stimulation. Knockdown of ATF2 or ATF7 decreases the rate of cell proliferation and the number of cells in M-phase. In particular, the knockdown of ATF7 severely inhibits cell proliferation and G2/M progression. The inducible expression of a mitotically nonphosphorylatable version of ATF7 inhibits G2/M progression despite the presence of endogenous ATF7. We also show that mitotic phosphorylation of ATF7 promotes the activation of Aurora kinases, which are key enzymes for early mitotic events. These results suggest that the Cdk1-mediated phosphorylation of ATF7 facilitates G2/M progression, at least in part, by enabling Aurora signaling.
Many animals fight for dominance between conspecifics. Because winners could obtain more resources than losers, fighting outcomes are important for the animal's survival, especially in a situation with insufficient resources, such as hunger. However, it remains unclear whether and how hunger affects fighting outcomes. Herein, we investigate the effects of food deprivation on brain activity and fighting behaviors in zebrafish. We report that starvation induces winning in social conflicts. Before the fights, starved fish show potentiation of the lateral subregion of the dorsal habenula (dHbL)-dorsal/intermediate interpeduncular nucleus (d/iIPN) pathway, which is known to be essential for and potentiated after winning fights. Circuit potentiation is mediated by hypothalamic orexin/hypocretin neuropeptides, which prolong AMPA-type glutamate receptor (AMPAR) activity by increasing the expression of a flip type of alternative splicing variant of the AMPAR subunit. This mechanism may underlie how hungry vertebrates win fights and may be commonly shared across animal phylogeny.
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