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Divergent Modulation of Proteostasis in Prostate Cancer

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Proteostasis and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1233))

Abstract

Proteostasis regulates key cellular processes such as cell proliferation, differentiation, transcription, and apoptosis. The mechanisms by which proteostasis is regulated are crucial and the deterioration of cellular proteostasis has been significantly associated with tumorigenesis since it specifically targets key oncoproteins and tumor suppressors. Prostate cancer (PCa) is the second most common cause of cancer death in men worldwide. Androgens mediate one of the most central signaling pathways in all stages of PCa via the androgen receptor (AR). In addition to their regulation by hormones, PCa cells are also known to be highly secretory and are particularly prone to ER stress as proper ER function is essential. Alterations in various complex signaling pathways and cellular processes including cell cycle control, transcription, DNA repair, apoptosis, cell adhesion, epithelial–mesenchymal transition (EMT), and angiogenesis are critical factors influencing PCa development through key molecular changes mainly by posttranslational modifications in PCa-related proteins, including AR, NKX3.1, PTEN, p53, cyclin D1, and p27. Several ubiquitin ligases like MDM2, Siah2, RNF6, CHIP, and substrate-binding adaptor SPOP; deubiquitinases such as USP7, USP10, USP26, and USP12 are just some of the modifiers involved in the regulation of these key proteins via ubiquitin–proteasome system (UPS). Some ubiquitin-like modifiers, especially SUMOs, have been also closely associated with PCa. On the other hand, the proteotoxicity resulting from misfolded proteins and failure of ER adaptive capacity induce unfolded protein response (UPR) that is an indispensable signaling mechanism for PCa development. Lastly, ER-associated degradation (ERAD) also plays a crucial role in prostate tumorigenesis. In this section, the relationship between prostate cancer and proteostasis will be discussed in terms of UPS, UPR, SUMOylation, ERAD, and autophagy.

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Acknowledgments

Work by PBK is supported by the Scientific and Technological Research Council of Turkey (TUBITAK, SBAG-108S056/114S062), Ege University internal funds, BAGEP Award of the Science Academy with funding supplied by Pfizer-Turkey, COST Action (PROTEOSTASIS BM1307), and by COST (European Cooperation in Science and Technology).

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Biochemistry, Ege University, Izmir, Turkey

    Petek Ballar Kirmizibayrak

  2. Faculty of Science, Department of Molecular Biology and Genetic, Uludag University, Bursa, Turkey

    Burcu Erbaykent-Tepedelen

  3. Faculty of Medicine, Department of Physiology, Ege University, Izmir, Turkey

    Oguz Gozen

  4. Faculty of Pharmacy, Department of Biochemistry, Suleyman Demirel University, Isparta, Turkey

    Yalcin Erzurumlu

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  1. Petek Ballar Kirmizibayrak
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  1. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    Rosa Barrio

  2. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    James D. Sutherland

  3. Centre Pierre Potier, ITAV, Toulouse Cedex 1, France

    Manuel S. Rodriguez

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Ballar Kirmizibayrak, P., Erbaykent-Tepedelen, B., Gozen, O., Erzurumlu, Y. (2020). Divergent Modulation of Proteostasis in Prostate Cancer. In: Barrio, R., Sutherland, J., Rodriguez, M. (eds) Proteostasis and Disease . Advances in Experimental Medicine and Biology, vol 1233. Springer, Cham. https://doi.org/10.1007/978-3-030-38266-7_5

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