Sahu Indrajit, Nanaware Padma, Mane Minal, Mulla Saim Wasi, Roy Soumen, Venkatraman Prasanna
Advance Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel.
Int J Stem Cells. 2019 Nov 30;12(3):463-473. doi: 10.15283/ijsc19007.
PSMD10, a proteasome assembly chaperone, is a widely known oncoprotein which aspects many hall mark properties of cancer. However, except proteasome assembly chaperon function its role in normal cell function remains unknown. To address this issue, we induced PSMD10 overexpression in HEK293 cells and the resultant large-scale changes in gene expression profile were analyzed. We constituted networks from microarray data of these differentially expressed genes and carried out extensive topological analyses. The overrecurring yet consistent theme that appeared throughout analysis using varied network metrics is that all genes and interactions identified as important would be involved in neurogenesis and neuronal development. Intrigued we tested the possibility that PSMD10 may be strongly associated with cell fate decisions that commit neural stem cells to differentiate into neurons. Overexpression of PSMD10 in human neural progenitor cells facilitated neuronal differentiation via -catenin Ngn1 pathway. Here for the first time we provide preliminary and yet compelling experimental evidence for the involvement of a potential oncoprotein - PSMD10, in neuronal differentiation.
蛋白酶体组装分子伴侣PSMD10是一种广为人知的癌蛋白,它具有许多癌症的标志性特性。然而,除了蛋白酶体组装分子伴侣功能外,其在正常细胞功能中的作用仍不清楚。为了解决这个问题,我们在HEK293细胞中诱导PSMD10过表达,并分析由此产生的基因表达谱的大规模变化。我们根据这些差异表达基因的微阵列数据构建网络,并进行了广泛的拓扑分析。在使用各种网络指标的整个分析过程中出现的反复出现且一致的主题是,所有被确定为重要的基因和相互作用都将参与神经发生和神经元发育。受此启发,我们测试了PSMD10可能与促使神经干细胞分化为神经元的细胞命运决定密切相关的可能性。PSMD10在人类神经祖细胞中的过表达通过β-连环蛋白-Ngn1途径促进神经元分化。在此,我们首次为一种潜在的癌蛋白PSMD10参与神经元分化提供了初步但令人信服的实验证据。