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.
Keywords: CUL3; LZTR1; Noonan syndrome; RAS/MAPK signaling pathway; glioblastoma; ubiquitin ligase; ubiquitination.
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