ULK/Atg1的典型和非典型功能。
Canonical and noncanonical functions of ULK/Atg1.
作者信息
Wang Bo, Kundu Mondira
机构信息
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
出版信息
Curr Opin Cell Biol. 2017 Apr;45:47-54. doi: 10.1016/j.ceb.2017.02.011. Epub 2017 Mar 11.
Abstract
Mammalian Unc-51-like kinases 1 and 2 (ULK1 and ULK2) belong to the ULK/Atg1 family of serine/threonine kinases, which are conserved from yeast to mammals. Although ULK/Atg1 is best known for regulating flux through the autophagy pathway, it has evolutionarily conserved noncanonical functions in protein trafficking that are essential for maintaining cellular homeostasis. As a direct target of energy- and nutrient-sensing kinases, ULK/Atg1 is positioned to regulate the distribution and use of cellular resources in response to metabolic cues. In this review, we provide an overview of the molecular mechanisms through which ULK/Atg1 carries out its canonical and noncanonical functions and the signaling pathways that link its function to metabolism. We also highlight potential contributions of ULK/Atg1 in human diseases, including cancer and neurodegeneration.
摘要
哺乳动物Unc-51样激酶1和2（ULK1和ULK2）属于丝氨酸/苏氨酸激酶的ULK/Atg1家族，该家族在从酵母到哺乳动物中都是保守的。尽管ULK/Atg1最出名的是调节自噬途径的通量，但它在蛋白质运输中具有进化上保守的非经典功能，这些功能对于维持细胞内稳态至关重要。作为能量和营养感应激酶的直接靶点，ULK/Atg1能够根据代谢信号调节细胞资源的分配和利用。在这篇综述中，我们概述了ULK/Atg1执行其经典和非经典功能的分子机制，以及将其功能与代谢联系起来的信号通路。我们还强调了ULK/Atg1在包括癌症和神经退行性疾病在内的人类疾病中的潜在作用。
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