AMBRA1的CDK1和PLK1磷酸化调节有丝分裂纺锤体定向。
AMBRA1 phosphorylation by CDK1 and PLK1 regulates mitotic spindle orientation.
发表日期：2023 Aug 16
作者：
Fiorella Faienza, Federica Polverino, Girish Rajendraprasad, Giacomo Milletti, Zehan Hu, Barbara Colella, Deborah Gargano, Flavie Strappazzon, Salvatore Rizza, Mette Vixø Vistesen, Yonglun Luo, Manuela Antonioli, Valentina Cianfanelli, Caterina Ferraina, Gian Maria Fimia, Giuseppe Filomeni, Daniela De Zio, Joern Dengjel, Marin Barisic, Giulia Guarguaglini, Sabrina Di Bartolomeo, Francesco Cecconi
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
AMBRA1 是神经系统发育的重要因子，它的功能主要与自噬相关。它还与细胞增殖调控有关，通过调节 c-Myc 和 D 型细胞周期蛋白的水平，从而调控 G1-S 过渡。然而，关于 AMBRA1 在细胞周期中是否差异调控及其促自噬蛋白是否在调控有丝分裂过程中起直接作用，仍然不清楚。在这里我们展示了 AMBRA1 在有丝分裂中被 CDK1 和 PLK1 这两个有丝分裂激酶磷酸化，并且有多个磷酸化位点。此外，我们证明了 AMBRA1 在有丝分裂中的磷酸化对于适当的纺锤体功能和定向是必需的，这是由 NUMA1 蛋白驱动的。实际上，我们展示了 NUMA1 的定位和/或动力学严格依赖于 AMBRA1 存在、磷酸化和结合能力。由于纺锤体定向对于组织形态发生和分化至关重要，我们的发现可能说明了 AMBRA1 在发育和癌症发生过程中的额外作用。© 2023. 作者.
AMBRA1 is a crucial factor for nervous system development, and its function has been mainly associated with autophagy. It has been also linked to cell proliferation control, through its ability to regulate c-Myc and D-type cyclins protein levels, thus regulating G1-S transition. However, it remains still unknown whether AMBRA1 is differentially regulated during the cell cycle, and if this pro-autophagy protein exerts a direct role in controlling mitosis too. Here we show that AMBRA1 is phosphorylated during mitosis on multiple sites by CDK1 and PLK1, two mitotic kinases. Moreover, we demonstrate that AMBRA1 phosphorylation at mitosis is required for a proper spindle function and orientation, driven by NUMA1 protein. Indeed, we show that the localization and/or dynamics of NUMA1 are strictly dependent on AMBRA1 presence, phosphorylation and binding ability. Since spindle orientation is critical for tissue morphogenesis and differentiation, our findings could account for an additional role of AMBRA1 in development and cancer ontogenesis.© 2023. The Author(s).