PDF(Pubmed)
Abstract：
The study of the disorders of ubiquitin-mediated proteasomal degradation may unravel the molecular basis of human diseases, such as cancer (prostate cancer, lung cancer and liver cancer, etc.) and nervous system disease (Parkinson\'s disease, Alzheimer\'s disease and Huntington\'s disease, etc.) and help in the design of new therapeutic methods. Leucine zipper-like transcription regulator 1 (LZTR1) is an important substrate recognition subunit of cullin-RING E3 ligase that plays an important role in the regulation of cellular functions. Mutations in LZTR1 and dysregulation of associated downstream signaling pathways contribute to the pathogenesis of Noonan syndrome (NS), glioblastoma and chronic myeloid leukemia. Understanding the molecular mechanism of the normal function of LZTR1 is thus critical for its eventual therapeutic targeting. In the present review, the structure and function of LZTR1 are described. Moreover, recent advances in the current knowledge of the functions of LZTR1 in NS, glioblastoma (GBM), chronic myeloid leukemia (CML) and schwannomatosis and the influence of LZTR1 mutations are also discussed, providing insight into how LZTR1 may be targeted for therapeutic purposes.
摘要：
泛素介导的蛋白酶体降解紊乱的研究可能揭示人类疾病的分子基础,如癌症（前列腺癌，肺癌和肝癌，等。)和神经系统疾病(帕金森病，阿尔茨海默病和亨廷顿病,等。)并帮助设计新的治疗方法。亮氨酸拉链样转录调节因子1（LZTR1）是cullin-RINGE3连接酶的重要底物识别亚基，在细胞功能调节中起重要作用。LZTR1的突变和相关下游信号通路的失调有助于Noonan综合征（NS）的发病机理，胶质母细胞瘤和慢性粒细胞白血病。因此，了解LZTR1正常功能的分子机制对于其最终的治疗靶向至关重要。在本次审查中，描述了LZTR1的结构和功能。此外，关于LZTR1在NS中的功能的当前知识的最新进展，胶质母细胞瘤（GBM），还讨论了慢性粒细胞白血病（CML）和神经鞘瘤病以及LZTR1突变的影响，深入了解LZTR1如何靶向治疗目的。
