Kırmızıbayrak, Petek BallarGözen, OğuzErzurumlu, YalçınBarrio, RSutherland, JDRodriguez, MS2023-02-132023-02-132020-04-10Kırmızıbayrak, P. B. vd. (2020). "Divergent modulation of proteostasis in prostate cancer". ed. R. Barrio vd. Advances in Experimental Medicine and Biology, 1233, 117-151.978-3-030-38265-0978-3-030-38266-70065-25982214-8019https://doi.org/10.1007/978-3-030-38266-7_5https://link.springer.com/chapter/10.1007/978-3-030-38266-7_5http://hdl.handle.net/11452/30992Proteostasis 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.eninfo:eu-repo/semantics/closedAccessBiochemistry & molecular biologyPathologyResearch & experimental medicineProstate cancerUbiquitinUbiquitin-likeDeubiquitinaseAutophagyUnfolded protein responseUnfolded protein responseAndrogen receptor-activtyTumor-suppressor geneDeubiquitinating enzyme USP12Ubiquitin ligase SIAH2Heat-shock proteinsWild-type spopCell-proliferationHomeobox geneTranscriptional activityDeubiquitinating enzymesEndoplasmic reticulum-associated degradationHumansMaleProstatic neoplasmsProteasome endopeptidase complexProteostasisUbiquitinUnfolded protein responseArticle0005308386000062-s2.0-85083257850117151123332274755Biochemistry & molecular biologyPathologyMedicine, research & experimentalDeubiquitinase; Ubiquitin-Specific Proteases; UbiquitinAndrogenAndrogen receptorCell nucleus receptorCullin RING ubiquitin ligaseCyclin D1Cyclin dependent kinase inhibitor 1BLigaseMyc proteinPhosphatidylinositol 3 kinasePhosphatidylinositol 3,4,5 trisphosphate 3 phosphataseProstate specific antigenProtein kinase BProtein NKX 3 1Protein p21Protein p27Regulator proteinRING finger E3 ubiquitin ligaseUbiquitinUbiquitin protein ligase E3Ubiquitin protein ligase NEDD4Unclassified drugDeubiquitinaseProteasomeUbiquitinAmino acid sequenceAmino terminal sequenceAutophagy (cellular)Cancer inhibitionCarboxy terminal sequenceCarcinogenesisDeubiquitinationDNA repairEndoplasmic reticulum associated degradationEpithelial mesenchymal transitionHumanNonhumanOncogene mycPriority journalProstate cancerProtein expressionProtein functionProtein homeostasisSumoylationUbiquitinationUnfolded protein responseEnzymologyMaleMetabolismProstate tumor