Hong‑Ping Zhu

Peripheral myelin protein 22 (PMP22) and epithelial membrane proteins (EMP-1, -2, and -3) belong to a small hydrophobic membrane protein subfamily, with four transmembrane structures. PMP22 and EMPs are widely expressed in various tissues and play important roles in cell growth, differentiation, programmed cell death, and metastasis. PMP22 presents its highest expression in the peripheral nerve and participates in normal physiological and pathological processes of the peripheral nervous system. The progress of molecular genetics has shown that the genetic changes of the PMP22 gene, including duplication, deletion, and point mutation, are behind various hereditary peripheral neuropathies. EMPs have different expression patterns in diverse tissues and are closely related to the risk of malignant tumor progression. In this review, we focus on the four members in this protein family which are related to disease pathogenesis and discuss gene mutations and post-translational modification of them. Further research into the interactions between structural alterations and function of PMP22 and EMPs will help understand their normal physiological function and role in diseases and might contribute to developing novel therapeutic tools.

Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor.