Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer
Prostate cancer (PCa) is the most commonly diagnosed cancer among men in western countries. Androgen receptor (AR) signaling plays key roles in the development of PCa. Androgen deprivation therapy (ADT) remains the standard therapy for advanced PCa. In addition to its ligand androgen, accumulating e...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-07-01
|
| Series: | Asian Journal of Urology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214388219301110 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849766776742608896 |
|---|---|
| author | Simeng Wen Yuanjie Niu Haojie Huang |
| author_facet | Simeng Wen Yuanjie Niu Haojie Huang |
| author_sort | Simeng Wen |
| collection | DOAJ |
| description | Prostate cancer (PCa) is the most commonly diagnosed cancer among men in western countries. Androgen receptor (AR) signaling plays key roles in the development of PCa. Androgen deprivation therapy (ADT) remains the standard therapy for advanced PCa. In addition to its ligand androgen, accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa, especially in castration resistant prostate cancer (CRPC). To date, a number of posttranscriptional modifications of AR have been identified, including phosphorylation (e.g. by CDK1), acetylation (e.g. by p300 and recognized by BRD4), methylation (e.g. by EZH2), ubiquitination (e.g. by SPOP), and SUMOylation (e.g. by PIAS1). These modifications are essential for the maintenance of protein stability, nuclear localization and transcriptional activity of AR. This review summarizes posttranslational modifications that influence androgen-dependent and -independent activities of AR, PCa progression and therapy resistance. We further emphasize that in addition to androgen, posttranslational modification is another important way to regulate AR activity, suggesting that targeting AR posttranslational modifications, such as proteolysis targeting chimeras (PROTACs) of AR, represents a potential and promising alternate for effective treatment of CRPC. Potential areas to be investigated in the future in the field of AR posttranslational modifications are also discussed. |
| format | Article |
| id | doaj-art-b09eec14e67c414cbea5416730ba8a0c |
| institution | DOAJ |
| issn | 2214-3882 |
| language | English |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Urology |
| spelling | doaj-art-b09eec14e67c414cbea5416730ba8a0c2025-08-20T03:04:29ZengElsevierAsian Journal of Urology2214-38822020-07-017320321810.1016/j.ajur.2019.11.001Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancerSimeng Wen0Yuanjie Niu1Haojie Huang2Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, USADepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China; Corresponding author.Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, USA; Department of Urology, Mayo Clinic College of Medicine and Science, Rochester, USA; Mayo Clinic Cancer Center, Mayo Clinic College of Medicine and Science, Rochester, USA; Corresponding author. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, USA.Prostate cancer (PCa) is the most commonly diagnosed cancer among men in western countries. Androgen receptor (AR) signaling plays key roles in the development of PCa. Androgen deprivation therapy (ADT) remains the standard therapy for advanced PCa. In addition to its ligand androgen, accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa, especially in castration resistant prostate cancer (CRPC). To date, a number of posttranscriptional modifications of AR have been identified, including phosphorylation (e.g. by CDK1), acetylation (e.g. by p300 and recognized by BRD4), methylation (e.g. by EZH2), ubiquitination (e.g. by SPOP), and SUMOylation (e.g. by PIAS1). These modifications are essential for the maintenance of protein stability, nuclear localization and transcriptional activity of AR. This review summarizes posttranslational modifications that influence androgen-dependent and -independent activities of AR, PCa progression and therapy resistance. We further emphasize that in addition to androgen, posttranslational modification is another important way to regulate AR activity, suggesting that targeting AR posttranslational modifications, such as proteolysis targeting chimeras (PROTACs) of AR, represents a potential and promising alternate for effective treatment of CRPC. Potential areas to be investigated in the future in the field of AR posttranslational modifications are also discussed.http://www.sciencedirect.com/science/article/pii/S2214388219301110Androgen receptorPosttranslational modificationPhosphorylationAcetylationMethylationUbiquitination |
| spellingShingle | Simeng Wen Yuanjie Niu Haojie Huang Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer Asian Journal of Urology Androgen receptor Posttranslational modification Phosphorylation Acetylation Methylation Ubiquitination |
| title | Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer |
| title_full | Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer |
| title_fullStr | Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer |
| title_full_unstemmed | Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer |
| title_short | Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer |
| title_sort | posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer |
| topic | Androgen receptor Posttranslational modification Phosphorylation Acetylation Methylation Ubiquitination |
| url | http://www.sciencedirect.com/science/article/pii/S2214388219301110 |
| work_keys_str_mv | AT simengwen posttranslationalregulationofandrogendependentandindependentandrogenreceptoractivitiesinprostatecancer AT yuanjieniu posttranslationalregulationofandrogendependentandindependentandrogenreceptoractivitiesinprostatecancer AT haojiehuang posttranslationalregulationofandrogendependentandindependentandrogenreceptoractivitiesinprostatecancer |