School of Biomedical Science, Faculty of Medicine, University of Queensland, St Lucia, Queensland 4067, Australia.
ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 260, Australia.
Biochim Biophys Acta Mol Cell Res. 2020 Jul;1867(7):118713. doi: 10.1016/j.bbamcr.2020.118713. Epub 2020 Apr 1.
WD40-Repeat Protein 62 (WDR62) is required to maintain neural and glial cell populations during embryonic brain growth. Although elevated expression of WDR62 is frequently associated with several tumour types, potential effects of excess WDR62 on proliferative growth remain undefined. Here, we demonstrate that glia specific overexpression of WDR62 in Drosophila larval brains resulted in increased cell size, over-proliferation and increased brain volume, without overt disruption of tissue organization. We further demonstrate WDR62 promoted over-proliferation and brain overgrowth by activating AURKA and pAKT signalling to increase MYC function in glial cells. Together these data suggest WDR62 normally functions in the glial lineage to activate oncogenic signalling networks, promoting proliferation and brain overgrowth.
WD40 重复蛋白 62（WDR62）在胚胎大脑生长过程中对于维持神经和神经胶质细胞群体至关重要。尽管 WDR62 的高表达常常与几种肿瘤类型相关联，但过量 WDR62 对增殖生长的潜在影响尚未确定。在这里，我们证明了在果蝇幼虫大脑中特异性过表达 WDR62 会导致细胞大小增加、过度增殖和大脑体积增加，而组织结构没有明显破坏。我们进一步证明，WDR62 通过激活 AURKA 和 pAKT 信号来增加 MYC 在神经胶质细胞中的功能，从而促进过度增殖和大脑过度生长。这些数据表明，WDR62 在神经胶质谱系中正常发挥作用，激活致癌信号网络，促进增殖和大脑过度生长。
