Bertini Teixeira Mariana, Figueira Ana Carolina M, Furlan Ariane S, Aquino Bruno, Alborghetti Marcos R, Paes Leme Adriana F, Wei Li-Na, Kobarg Jörg
Department of Biochemistry and Tissue Biology Institute of Biology University of Campinas Brazil.
Spectroscopy and Calorimetry Laboratory Brazilian Biosciences National Laboratory Center for Research in Energy and Materials Campinas SP Brazil.
FEBS Open Bio. 2017 Dec 9;8(1):4-14. doi: 10.1002/2211-5463.12338. eCollection 2018 Jan.
Fasciculation and elongation zeta-1 (FEZ1) protein is involved in axon outgrowth and is highly expressed in the brain. It has multiple interaction partners, with functions varying from the regulation of neuronal development and intracellular transport mechanisms to transcription regulation. One of its interactors is retinoic acid receptor (RAR), which is activated by retinoic acid and controls many target genes and physiological process. Based on previous evidence suggesting a possible nuclear role for FEZ1, we wanted to deepen our understanding of this function by addressing the FEZ1-RAR interaction. We performed binding experiments and assessed the interface of interaction between both proteins. We found that FEZ1-RAR interacted with a similar magnitude as RAR to its responsive element DR5 and that the interaction occurred in the coiled-coil region of FEZ1 and in the ligand-binding domain of RAR. Furthermore, cellular experiments were performed in order to confirm the interaction and screen for induced target genes from an 86-gene panel. The analysis of gene expression showed that only in the presence of retinoic acid did FEZ1 induce gene expression. This finding is consistent with data from the literature showing the gene functionally involved in development and acute myeloid leukemia, as is FEZ1.
束状延伸蛋白ζ-1（FEZ1）参与轴突生长，在大脑中高度表达。它有多个相互作用伙伴，其功能从调节神经元发育、细胞内运输机制到转录调控各不相同。它的一个相互作用蛋白是视黄酸受体（RAR），该受体被视黄酸激活并控制许多靶基因和生理过程。基于之前表明FEZ1可能在细胞核中发挥作用的证据，我们想通过研究FEZ1-RAR相互作用来加深对这一功能的理解。我们进行了结合实验，并评估了两种蛋白质之间的相互作用界面。我们发现FEZ1-RAR与RAR与其反应元件DR5的相互作用强度相似，且这种相互作用发生在FEZ1的卷曲螺旋区域和RAR的配体结合结构域。此外，为了证实这种相互作用并从一个86个基因的面板中筛选出诱导的靶基因，我们进行了细胞实验。基因表达分析表明，只有在视黄酸存在的情况下，FEZ1才会诱导基因表达。这一发现与文献数据一致，文献表明该基因在发育和急性髓系白血病中发挥功能作用，FEZ1也是如此。
