Yang Tiejun, Jing Yifeng, Dong Jun, Yu Xinpei, Zhong Mingming, Pascal Laura E, Wang Dan, Zhang Zhongxian, Qiao Baoping, Wang Zhou
Department of Urology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Prostate. 2018 Nov;78(15):1201-1212. doi: 10.1002/pros.23695. Epub 2018 Jul 15.
Elongation factor for RNA polymerase 2 (ELL2) and ELL associated factor 2 (EAF2) have been reported to have tumor suppressive properties in prostate epithelial cells.
We investigated ELL2 expression in human prostate cancer specimens, and ELL2 protein stability and ubiquitination in prostate cancer cells.
Immunostaining analysis of human prostate cancer specimens was used to determine ELL2 expression in tumor and normal tissues. ELL2 knockdown in prostate cancer cell lines LNCaP and C4-2 was used to compare proliferation and motility. Deletion and site-directed mutagenesis was used to identify amino acid residues in ELL2 that were important for degradation.
ELL2 protein was downregulated in prostate cancer specimens and was up-regulated by androgens in prostate cancer cell lines LNCaP and C4-2. ELL2 knockdown enhanced prostate cancer cell proliferation and motility. ELL2 protein has a short half-life and was stabilized by proteasome inhibitor MG132. Amino acid residues K584 and K599 in ELL2 were important for ELL2 degradation. EAF2 could stabilize ELL2 and inhibited its polyubiquitination.
Our findings provide further evidence that ELL2 is a potential tumor suppressor frequently down-regulated in clinical prostate cancer specimens and provides new insights into regulation of ELL2 protein level by polyubiquitination and EAF2 binding.
据报道，RNA聚合酶2延伸因子（ELL2）和ELL相关因子2（EAF2）在前列腺上皮细胞中具有肿瘤抑制特性。
我们研究了ELL2在人前列腺癌标本中的表达，以及ELL2蛋白在前列腺癌细胞中的稳定性和泛素化。
用人前列腺癌标本进行免疫染色分析，以确定ELL2在肿瘤组织和正常组织中的表达。在前列腺癌细胞系LNCaP和C4-2中敲低ELL2，以比较细胞增殖和迁移能力。采用缺失和定点诱变来鉴定ELL2中对降解重要的氨基酸残基。
ELL2蛋白在前列腺癌标本中下调，在前列腺癌细胞系LNCaP和C4-2中受雄激素上调。敲低ELL2可增强前列腺癌细胞的增殖和迁移能力。ELL2蛋白半衰期短，蛋白酶体抑制剂MG132可使其稳定。ELL2中的氨基酸残基K584和K599对ELL2降解很重要。EAF2可稳定ELL2并抑制其多聚泛素化。
我们的研究结果进一步证明ELL2是一种潜在的肿瘤抑制因子，在临床前列腺癌标本中经常下调，并为通过多聚泛素化和EAF2结合调节ELL2蛋白水平提供了新的见解。
