Abstract
Multiple studies have confirmed that speckle-type pox virus and zinc finger (POZ) protein (SPOP) functions as a substrate adaptor of cullin 3-based E3 ligase and has a crucial role in various cellular processes via specific targeting of proteins for ubiquitination and subsequent proteasomal degradation. Dysregulation of SPOP-mediated proteolysis might be involved in the development and progression of human prostate and kidney cancers. In prostate cancer, SPOP seems to function as a tumour suppressor by targeting several proteins, including androgen receptor (AR), steroid receptor coactivator 3 (SRC3) and BRD4, for degradation, whereas it might function as an oncoprotein in kidney cancer, for example, by targeting phosphatase and tensin homologue (PTEN) for proteasomal degradation. In addition, nuclear SPOP targets AR for degradation and has a role as a tumour suppressor in prostate cancer; however, in kidney cancer, SPOP largely accumulates in the cytoplasm and fails to promote degradation of AR located in the nucleus, resulting in activation of AR-driven pathways and cancer progression. Owing to the context-dependent function of SPOP in human malignancies, further assessment of the molecular mechanisms involving SPOP in prostate and kidney cancers is needed to improve our understanding of its role in the development of these cancer types. Treatments that target SPOP might become therapeutic strategies in these malignancies in the future.
Key points
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Speckle-type pox virus and zinc finger (POZ) protein (SPOP) is a substrate adaptor of cullin 3-based E3 ligase and targets multiple substrates with important biological functions in a plethora of cellular processes for ubiquitination and proteasomal degradation.
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SPOP dysregulation occurs in various cancer types, including prostate cancer and kidney cancer; as SPOP controls the turnover of key cellular signalling factors, dysregulation leads to abnormal regulation in cell proliferation, apoptosis, cell cycle, motility and metastasis.
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SPOP can have oncogenic and tumour-suppressive functions in a tissue-specific manner; SPOP seems to function as a tumour suppressor in prostate cancer but as an oncoprotein in kidney cancer.
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In prostate cancer, SPOP targets multiple oncoproteins, such as androgen receptor (AR), Cdc20, Myc, ERG, steroid receptor coactivator 3 (SRC3), PDL1 and BRD4, for degradation, whereas it controls the turnover of several tumour suppressors in renal cell carcinoma, including phosphatase and tensin homologue (PTEN), Daxx and DUSP7.
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Targeting SPOP might be a promising strategy for prevention or therapy of human cancers, such as prostate cancer.
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Acknowledgements
The authors’ research was supported in part by the Key Project from the Natural Science Foundation of Education Department of Anhui Province (KJ2019ZD27) and the Science and Technology Planning Project of Wenzhou City (Y20180082) and the Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation.
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Wang, Z., Song, Y., Ye, M. et al. The diverse roles of SPOP in prostate cancer and kidney cancer. Nat Rev Urol 17, 339–350 (2020). https://doi.org/10.1038/s41585-020-0314-z
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DOI: https://doi.org/10.1038/s41585-020-0314-z
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