PDF(Pubmed)
Abstract：
In this review we examine the functionally diverse ATPase associated with various cellular activities (AAA-ATPase), valosin-containing protein (VCP/p97), its molecular functions, the mutational landscape of VCP and the phenotypic manifestation of VCP disease. VCP is crucial to a multitude of cellular functions including protein quality control, endoplasmic reticulum-associated degradation (ERAD), autophagy, mitophagy, lysophagy, stress granule formation and clearance, DNA replication and mitosis, DNA damage response including nucleotide excision repair, ATM- and ATR-mediated damage response, homologous repair and non-homologous end joining. VCP variants cause multisystem proteinopathy, and pathology can arise in several tissue types such as skeletal muscle, bone, brain, motor neurons, sensory neurons and possibly cardiac muscle, with the disease course being challenging to predict.
摘要：
在这篇综述中，我们研究了与各种细胞活动相关的功能多样的ATPase（AAA-ATPase），含valosin蛋白（VCP/p97），它的分子功能，VCP的突变景观和VCP病的表型表现。VCP对包括蛋白质质量控制在内的多种细胞功能至关重要。内质网相关降解（ERAD），自噬,线粒体自噬,自噬，应力颗粒的形成和清除，DNA复制和有丝分裂,DNA损伤反应包括核苷酸切除修复，ATM和ATR介导的损伤反应，同源修复和非同源末端连接。VCP变异导致多系统蛋白病，和病理可以出现在几种组织类型，如骨骼肌，骨头,大脑,运动神经元,感觉神经元和心肌，疾病的进程是具有挑战性的预测。
