The MATH-BTB BPM3 and BPM5 subunits of Cullin3-RING E3 ubiquitin ligases target PP2CA and other clade A PP2Cs for degradation
The MATH-BTB BPM3 and BPM5 subunits of Cullin3-RING E3 ubiquitin ligases target PP2CA and other clade A PP2Cs for degradation
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DOI：
10.1073/pnas.1908677116
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发表时间：
2019-07-30
影响因子：
11.1
通讯作者：
Rodriguez, Pedro L.
中科院分区：
文献类型：
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作者：
Julian, Jose;Coego, Alberto;Rodriguez, Pedro L.
早期脱落酸信号传导涉及进化枝A蛋白磷酸酶2C型（PP2C）的降解，作为PYR/PYL/RCAR介导的PP2C活性抑制的补充机制。在随后的步骤中，ABA作为负反馈机制诱导PP2C转录物和蛋白质水平的上调。因此，ABA信号的重置也需要PP2C降解，以避免ABA诱导的PP2C过度积累。已经证明ABA分别通过PUB 12/13和RGLG 1/5 E3连接酶诱导现有ABI1和PP2CA的降解。然而，预测其他未鉴定的E3连接酶也调节进化枝A PP2C的蛋白质稳定性。在这项工作中，我们确定了BTB/POZ和MATH结构域蛋白（BPM），多聚cullin 3（CUL3）-RING为基础的E3连接酶（CRL 3）的底物衔接子，作为PP2CA相互作用蛋白。BPM3和BPM5在细胞核中与PP2CA以及ABI1、ABI2和HAB1相互作用。BPM3和BPM5以ABA依赖的方式加速PP2Cs的周转，并且它们的过表达导致ABA敏感性增强，而bpm3 bpm5植物显示PP2CA、ABI1和HAB1的积累增加，这导致ABA敏感性整体降低。利用生化和遗传分析，我们证明了PP2CA的泛素化依赖于BPM功能。鉴于受体ABA磷酸酶三元复合物的形成显着影响的蛋白质组分和ABA浓度的丰度，我们揭示了BPM和多聚体CRL 3 E3连接酶是重要的PP2C辅助受体水平的调节剂，以调节早期ABA信号传导以及后来的脱敏重置步骤。
Early abscisic acid signaling involves degradation of clade A protein phosphatases type 2C (PP2Cs) as a complementary mechanism to PYR/PYL/RCAR-mediated inhibition of PP2C activity. At later steps, ABA induces up-regulation of PP2C transcripts and protein levels as a negative feedback mechanism. Therefore, resetting of ABA signaling also requires PP2C degradation to avoid excessive ABA-induced accumulation of PP2Cs. It has been demonstrated that ABA induces the degradation of existing ABI1 and PP2CA through the PUB12/13 and RGLG1/5 E3 ligases, respectively. However, other unidentified E3 ligases are predicted to regulate protein stability of clade A PP2Cs as well. In this work, we identified BTB/POZ AND MATH DOMAIN proteins (BPMs), substrate adaptors of the multimeric cullin3 (CUL3)-RING-based E3 ligases (CRL3s), as PP2CA-interacting proteins. BPM3 and BPM5 interact in the nucleus with PP2CA as well as with ABI1, ABI2, and HAB1. BPM3 and BPM5 accelerate the turnover of PP2Cs in an ABA-dependent manner and their overexpression leads to enhanced ABA sensitivity, whereas bpm3 bpm5 plants show increased accumulation of PP2CA, ABI1 and HAB1, which leads to global diminished ABA sensitivity. Using biochemical and genetic assays, we demonstrated that ubiquitination of PP2CA depends on BPM function. Given the formation of receptor-ABA-phosphatase ternary complexes is markedly affected by the abundance of protein components and ABA concentration, we reveal that BPMs and multimeric CRL3 E3 ligases are important modulators of PP2C coreceptor levels to regulate early ABA signaling as well as the later desensitizing-resetting steps.