Ye Yihong, Tang Wai Kwan, Zhang Ting, Xia Di
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesda, MD, United States.
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of HealthBethesda, MD, United States.
Front Mol Biosci. 2017 Jun 13;4:39. doi: 10.3389/fmolb.2017.00039. eCollection 2017.
p97/VCP (known as Cdc48 in or TER94 in ) is one of the most abundant cytosolic ATPases. It is highly conserved from archaebacteria to eukaryotes. In conjunction with a large number of cofactors and adaptors, it couples ATP hydrolysis to segregation of polypeptides from immobile cellular structures such as protein assemblies, membranes, ribosome, and chromatin. This often results in proteasomal degradation of extracted polypeptides. Given the diversity of p97 substrates, this "segregase" activity has profound influence on cellular physiology ranging from protein homeostasis to DNA lesion sensing, and mutations in p97 have been linked to several human diseases. Here we summarize our current understanding of the structure and function of this important cellular machinery and discuss the relevant clinical implications.
p97/VCP（在酵母中称为Cdc48，在果蝇中称为TER94）是最丰富的胞质ATP酶之一。从古细菌到真核生物，它高度保守。它与大量辅助因子和衔接蛋白协同作用，将ATP水解与多肽从固定的细胞结构（如蛋白质聚集体、膜、核糖体和染色质）中分离出来。这通常导致被提取多肽的蛋白酶体降解。鉴于p97底物的多样性，这种“分离酶”活性对从蛋白质稳态到DNA损伤感应的细胞生理学有深远影响，并且p97中的突变与几种人类疾病有关。在这里，我们总结了目前对这种重要细胞机制的结构和功能的理解，并讨论了相关的临床意义。
