Regulating Androgen Receptor Function in Prostate Cancer: Exploring the Diversity of Post-Translational Modifications

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2024 Jan 26

PMID 38275816

Authors

Lance Edward V Lumahan

Mazia Arif

Amy E Whitener

Ping Yi

Affiliations

Soon will be listed here.

Abstract

Androgen receptor (AR) transcriptional activity significantly influences prostate cancer (PCa) progression. In addition to ligand stimulation, AR transcriptional activity is also influenced by a variety of post-translational modifications (PTMs). A number of oncogenes and tumor suppressors have been observed leveraging PTMs to influence AR activity. Subjectively targeting these post-translational modifiers based on their impact on PCa cell proliferation is a rapidly developing area of research. This review elucidates the modifiers, contextualizes the effects of these PTMs on AR activity, and connects these cellular interactions to the progression of PCa.

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References

Kaikkonen S, Jaaskelainen T, Karvonen U, Rytinki M, Makkonen H, Gioeli D . SUMO-specific protease 1 (SENP1) reverses the hormone-augmented SUMOylation of androgen receptor and modulates gene responses in prostate cancer cells. Mol Endocrinol. 2009; 23(3):292-307. PMC: 5428156. DOI: 10.1210/me.2008-0219. View

Mounir Z, Korn J, Westerling T, Lin F, Kirby C, Schirle M . ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor. Elife. 2016; 5. PMC: 4909395. DOI: 10.7554/eLife.13964. View

Chen S, Xu Y, Yuan X, Bubley G, Balk S . Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1. Proc Natl Acad Sci U S A. 2006; 103(43):15969-74. PMC: 1635111. DOI: 10.1073/pnas.0604193103. View

Gioeli D, Ficarro S, Kwiek J, Aaronson D, Hancock M, Catling A . Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. J Biol Chem. 2002; 277(32):29304-14. DOI: 10.1074/jbc.M204131200. View

Bunnell B, Heath L, Adams D, Lahti J, Kidd V . Increased expression of a 58-kDa protein kinase leads to changes in the CHO cell cycle. Proc Natl Acad Sci U S A. 1990; 87(19):7467-71. PMC: 54768. DOI: 10.1073/pnas.87.19.7467. View

Tyagi R, Lavrovsky Y, Ahn S, Song C, Chatterjee B, Roy A . Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells. Mol Endocrinol. 2000; 14(8):1162-74. DOI: 10.1210/mend.14.8.0497. View

Clinckemalie L, Vanderschueren D, Boonen S, Claessens F . The hinge region in androgen receptor control. Mol Cell Endocrinol. 2012; 358(1):1-8. DOI: 10.1016/j.mce.2012.02.019. View

Ponguta L, Gregory C, French F, Wilson E . Site-specific androgen receptor serine phosphorylation linked to epidermal growth factor-dependent growth of castration-recurrent prostate cancer. J Biol Chem. 2008; 283(30):20989-1001. PMC: 2475695. DOI: 10.1074/jbc.M802392200. View

Geiss-Friedlander R, Melchior F . Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol. 2007; 8(12):947-56. DOI: 10.1038/nrm2293. View

10.

Mohler J . A role for the androgen-receptor in clinically localized and advanced prostate cancer. Best Pract Res Clin Endocrinol Metab. 2008; 22(2):357-72. PMC: 2799036. DOI: 10.1016/j.beem.2008.01.009. View

11.

Gareau J, Lima C . The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition. Nat Rev Mol Cell Biol. 2010; 11(12):861-71. PMC: 3079294. DOI: 10.1038/nrm3011. View

12.

McClurg U, Summerscales E, Harle V, Gaughan L, Robson C . Deubiquitinating enzyme Usp12 regulates the interaction between the androgen receptor and the Akt pathway. Oncotarget. 2014; 5(16):7081-92. PMC: 4196185. DOI: 10.18632/oncotarget.2162. View

13.

van der Horst E, Degenhardt Y, Strelow A, Slavin A, Chinn L, Orf J . Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1. Proc Natl Acad Sci U S A. 2005; 102(44):15901-6. PMC: 1276100. DOI: 10.1073/pnas.0508014102. View

14.

Kobelyatskaya A, Pudova E, Katunina I, Snezhkina A, Fedorova M, Pavlov V . Transcriptome Profiling of Prostate Cancer, Considering Risk Groups and the TMPRSS2-ERG Molecular Subtype. Int J Mol Sci. 2023; 24(11). PMC: 10253008. DOI: 10.3390/ijms24119282. View

15.

Bawa-Khalfe T, Cheng J, Wang Z, Yeh E . Induction of the SUMO-specific protease 1 transcription by the androgen receptor in prostate cancer cells. J Biol Chem. 2007; 282(52):37341-9. DOI: 10.1074/jbc.M706978200. View

16.

Zhou Z, Kemppainen J, Wilson E . Identification of three proline-directed phosphorylation sites in the human androgen receptor. Mol Endocrinol. 1995; 9(5):605-15. DOI: 10.1210/mend.9.5.7565807. View

17.

Kotaja N, Karvonen U, Janne O, Palvimo J . The nuclear receptor interaction domain of GRIP1 is modulated by covalent attachment of SUMO-1. J Biol Chem. 2002; 277(33):30283-8. DOI: 10.1074/jbc.M204768200. View

18.

Drake J, Graham N, Stoyanova T, Sedghi A, Goldstein A, Cai H . Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression. Proc Natl Acad Sci U S A. 2012; 109(5):1643-8. PMC: 3277127. DOI: 10.1073/pnas.1120985109. View

19.

Lakshmikanthan V, Zou L, Kim J, Michal A, Nie Z, Messias N . Identification of betaArrestin2 as a corepressor of androgen receptor signaling in prostate cancer. Proc Natl Acad Sci U S A. 2009; 106(23):9379-84. PMC: 2695075. DOI: 10.1073/pnas.0900258106. View

20.

Samarzija I . Post-Translational Modifications That Drive Prostate Cancer Progression. Biomolecules. 2021; 11(2). PMC: 7915076. DOI: 10.3390/biom11020247. View