Tumor suppressor SPOP ubiquitinates and degrades Eg1N2 to compromise growth of prostate cancer cells

Eg1N prolyl hydroxylases, a family of oxygen-sensing enzymes, hydroxylate distinct proteins to modulate diverse physiopathological signals. Aberrant regulations of Eg1Ns result in multiple human diseases, including cancer. Different from Eg1N1 which function largely depends on the role of hypoxia-induce factor alpha (HIF alpha) in tumors, the functional significance and the upstream regulatory mechanisms of Eg1N2, especially in prostate cancer setting, remain largely unclear. Here, we demonstrated that dysregulation of Eg1N2 facilitated prostate cancer growth both in cells and in vivo. Notably, Eg1N2 was identified highly expressed in human prostate cancer tissues. Mechanically, Cullin 3-based E3 ubiquitin ligase SPOP, a well-characterized tumor suppressor in prostate cancer, could recognize and destruct Eg1N2. Meanwhile, androgen receptor (AR), playing a pivotal role in progression and development of prostate cancer, could transcriptionally up-regulate Eg1N2. Pathologically, SPOP loss-of-function mutations or AR amplification, frequently occurring in prostate cancers, could significantly accumulate Eg1N2 abundance. Therefore, our study not only underlines an oncogenic role of Eg1N2 in prostate cancer, but also highlights SPOP as a tumor suppressor to down-regulate Eg1N2 in prostate cancer. (C) 2017 Elsevier B.V. All rights reserved.