Department of Pathology, Harvard Medical School, Boston, MA USA.
Cell Cycle. 2010 Feb 1;9(3):482-5. doi: 10.4161/cc.9.3.10558.
The E3 ubiquitin ligases Cdc20-anaphase-promoting complex (Cdc20-APC) and Cdh1-APC play key roles in cell cycle transitions in proliferating cells. Remarkably, these ubiquitin ligases are also expressed in postmitotic neurons, raising interest in non-mitotic functions of the APC. Cdh1-APC has been implicated in diverse functions in the nervous system, from the control of axon growth and patterning to synapse development to neuron survival. However, until recently the question of whether Cdc20-APC harbors functions in neurons remained unanswered. New evidence from Kim et al. (2009) has uncovered a novel role for Cdc20-APCin dendrite growth and elaboration in post-mitotic neurons. Interestingly, the histone deacetylase HDAC6 augments Cdc20-APC activity at the centrosome by promoting Cdc20 polyubiquitination. In turn, Cdc20-APC triggers the degradation of the centrosomally localized protein Id1 and thereby promotes dendrite growth and elaboration. These findings have advanced our understanding of APC biology in neuronal connectivity in the brain.
E3 泛素连接酶 Cdc20-APC(细胞分裂周期蛋白 20-APC)和 Cdh1-APC 在增殖细胞的细胞周期转换中发挥关键作用。值得注意的是,这些泛素连接酶也在有丝分裂后神经元中表达,这引起了人们对 APC 非有丝分裂功能的兴趣。Cdh1-APC 已被牵涉到神经系统中的多种功能,从控制轴突生长和模式形成到突触发育再到神经元存活。然而,直到最近,Cdc20-APC 是否在神经元中具有功能的问题仍然没有答案。Kim 等人(2009)的新证据揭示了 Cdc20-APC 在有丝分裂后神经元的树突生长和细化中的新作用。有趣的是,组蛋白去乙酰化酶 HDAC6 通过促进 Cdc20 多泛素化来增强 Cdc20-APC 在中心体的活性。反过来,Cdc20-APC 触发定位于中心体的蛋白质 Id1 的降解,从而促进树突的生长和细化。这些发现推进了我们对 APC 生物学在大脑中神经元连接中的理解。