Paul Swagatika, Biswas Sahitya Ranjan, Milner Julia P, Tomsick Porter L, Pickrell Alicia M
Graduate Program in Biomedical and Veterinary Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Translational Biology, Medicine, and Health Graduate Program, Virginia Polytechnic Institute and State University, Roanoke, Virginia, USA.
Traffic. 2025 Jan-Mar;26(1-3):e70000. doi: 10.1111/tra.70000.
The serine/threonine kinase, Tank Binding Kinase 1 (TBK1), drives distinct cellular processes like innate immune signaling, selective autophagy, and mitosis. It is suggested that the translocation and activation of TBK1 at different subcellular locations within the cell, downstream of diverse stimuli, are driven by TBK1 adaptor proteins forming a complex directly or indirectly with TBK1. Various TBK1 adaptors and associated proteins like NAP1, TANK, SINTBAD, p62, optineurin (OPTN), TAX1BP1, STING, and NDP52 have been identified in facilitating TBK1 activation and recruitment with varying overlapping redundancy. This review focuses on what is known about these proteins, their interactions with TBK1, and the functional consequences of these associations. We shed light on underexplored areas of research on these TBK1 binding partners while emphasizing how future research is required to understand the function and flexibility of TBK1 signaling and crosstalk or regulation between different biological processes.
丝氨酸/苏氨酸激酶,即 Tank 结合激酶 1(TBK1),驱动着多种不同的细胞过程,如天然免疫信号传导、选择性自噬和有丝分裂。有人提出,在细胞内不同亚细胞位置,在多种刺激下游,TBK1 的易位和激活是由与 TBK1 直接或间接形成复合物的 TBK1 衔接蛋白驱动的。已经鉴定出多种 TBK1 衔接蛋白及相关蛋白,如 NAP1、TANK、SINTBAD、p62、视黄醛结合蛋白(OPTN)、TAX1BP1、干扰素基因刺激蛋白(STING)和 NDP52,它们在促进 TBK1 激活和募集方面具有不同程度的重叠冗余。本综述聚焦于对这些蛋白的已知信息、它们与 TBK1 的相互作用以及这些关联的功能后果。我们揭示了这些 TBK1 结合伙伴研究中未充分探索的领域,同时强调需要未来的研究来理解 TBK1 信号传导的功能和灵活性,以及不同生物过程之间的相互作用或调节。