Cyclin B3: an anaphase onset controller in meiosis

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Cyclin B3 controls anaphase onset independent of spindle assembly checkpoint in meiotic oocytes

The process of cell cycle has been studied with a long history, and molecular changings of each phase have also been well uncovered by previous studies. Proliferative cells pass through several checkpoints such as G1/S checkpoint, G2/M checkpoint and spindle assembly checkpoint (SAC) that control different key steps so that the cellular progression impelled under highly ordinary manner. While last 2 decades the scientists reported many important proteins or complexes which are involved in these checkpoint reactions, such as Cdc25, Cyclin B1, MCC and anaphase promoting complex/cyclosome (APC/C).¹ In meiosis, SAC was also shown to be essential for both female and male meiosis.² Besides SAC, APC/C is also an important controller of metaphase-anaphase transition: it controls cell cycle through ubiquitinating Cyclin B1 and Securin in a Cdc20-dependent manner, but its activation, especially in meiosis is still not clearly uncovered.³

Recently an article in Cell Cycle by Zhang T et al uncovered a new mechanism that controlled anaphase onset in oocyte meiosis I progression.⁴ Cyclin B3, a Cyclin family member that has been discovered recently is found to be a key controller of metaphase-anaphase transition in meiosis I. The Cyclin B3-knock down oocytes showed very poor ability of maturation; interestingly, this maturation blocking was not caused by SAC activation: the spindle assembled normally and SAC regulators BubR1 and Bub3 were confirmed to lose activity in right times. Then their insight came to APC/C, and they found APC/C function was inhibited, its substrate Cyclin B1 was not degraded after metaphase I. The rescue experiments by knock down of Mad2 and overexpression of Cdc20, the direct activator of APC/C showed negative effects on Cyclin B3-depleted oocytes. Their findings confirmed that SAC was not involved in the Cyclin B3-induced anaphase blocking and Cyclin B3 might be an activator of APC components. Moreover, they indicated that in the transition from metaphase I to anaphase I in female meiosis, after SAC loss activity Securin mostly controls the progression, while Cyclin B1 seems to be less important than we thought (Fig. 1).

Figure 1. Diagram of the roles and its signaling pathway of Cyclin B3 in oocyte meiosis.

Another recent work about Cyclin B3 showed that Cyclin B3 was an accelerator of anaphase onset in Drosophila embryos. Their theory was that: early Cyclins such as Cyclin A and Cyclin B1 stabilize Cyclin B3 until the right time, so that Cyclin B3 could promote cell cycle, and in late mitosis Cyclin B3 needs to be degraded, if not, cell cycle will be arrested.⁵ These two articles together showed us the important function of Cyclin B3 on anaphase onset, both in meiosis and mitosis. The current work by Zhang T et al. linked Cyclin B3 with APC/C activity, and they revealed preliminary mechanism of this novel anaphase controller in meiosis and provided direction of further research.