Regulation of the androgen receptor by post-translational modifications

Coffey, Kelly; Robson, Craig

doi:10.1530/joe-12-0238

Cited by 121 publications

(102 citation statements)

References 142 publications

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“…Increased expression of AR during initiation of prostate cancer might also drive a change in chromatin binding patterns that facilitate malignant proliferation. In recent years, a number of PTMs that alter AR activity have been discovered, including phosphorylation, acetylation, SUMOylation, methylation, and ubiquitination (Coffey & Robson 2012, Gioeli & Paschal 2012. Some PTMs have been implicated in malignant transformation.…”

Section: Ar In Prostate Cancer Initiationmentioning

confidence: 99%

Androgens and androgen receptor signaling in prostate tumorigenesis

Zhou¹,

Bolton²,

Jones³

2014

Journal of Molecular Endocrinology

165

112

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Androgens and androgen receptor (AR) signaling are necessary for prostate development and homeostasis. AR signaling also drives the growth of nearly all prostate cancer cells. The role of androgens and AR signaling has been well characterized in metastatic prostate cancer, where it has been shown that prostate cancer cells are exquisitely adept at maintaining functional AR signaling to drive cancer growth. As androgens and AR signaling are so intimately involved in prostate development and the proliferation of advanced prostate cancer, it stands to reason that androgens and AR are also involved in prostate cancer initiation and the early stages of cancer growth, yet little is known of this process. In this review, we summarize the current state of knowledge concerning the role of androgens and AR signaling in prostate tissue, from development to metastatic, castration-resistant prostate cancer, and use that information to suggest potential roles for androgens and AR in prostate cancer initiation.

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Section: Ar In Prostate Cancer Initiationmentioning

confidence: 99%

Androgens and androgen receptor signaling in prostate tumorigenesis

Zhou¹,

Bolton²,

Jones³

2014

Journal of Molecular Endocrinology

165

112

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“…AR is the target of several post-translational modifications including acetylation, phosphorylation, methylation, ubiquitination and sumoylation (reviewed in Coffey & Robson (2012)). AR sumoylation has been demonstrated to enrich AR in the nuclear matrix under conditions of cellular stress, causing attenuation of the transcriptional activity of AR, contributing to defective androgen signalling in cancer (Poukka et al 2000, Rytinki et al 2012.…”

Section: Structure and Function Of Arsmentioning

confidence: 99%

Evidence of androgen action in endometrial and ovarian cancers

Gibson

Simitsidellis

Collins

et al. 2014

Endocrine-Related Cancer

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Endometrial cancer (EC) and ovarian cancer are common gynaecological malignancies. The impact of androgen action in these cancers is poorly understood; however, there is emerging evidence to suggest that targeting androgen signalling may be of therapeutic benefit. Epidemiological evidence suggests that there is an increased risk of EC associated with exposure to elevated levels of androgens, and genetic variants in genes related to both androgen biosynthesis and action are associated with an increased risk of both EC and ovarian cancer. Androgen receptors (ARs) may be a potential therapeutic target in EC due to reported anti-proliferative activities of androgens. By contrast, androgens may promote growth of some ovarian cancers and anti-androgen therapy has been proposed. Introduction of new therapies targeting ARs expressed in EC or ovarian cancer will require a much greater understanding of the impacts of cell context-specific AR-dependent signalling and how ARs can crosstalk with other steroid receptors during progression of disease. This review considers the evidence that androgens may be important in the aetiology of EC and ovarian cancer with discussion of evidence for androgen action in normal and malignant endometrial and ovarian tissue.

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“…AR ubiquitination can also lead to the increase in transcriptional activity; RNF6 has been reported to ubiquitinate AR at Lys-845 and Lys-847, promoting its activity by allowing ARA54 co-activator recruitment (19). Further details of AR post-translational modifications have been recently reviewed (20).…”

mentioning

confidence: 99%

Deubiquitinating Enzyme Usp12 Is a Novel Co-activator of the Androgen Receptor

Burska¹,

Harle²,

Coffey

et al. 2013

Journal of Biological Chemistry

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111

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Background: Androgen receptor (AR) is the principle therapeutic target in prostate cancer. Result: We have established that Usp12 deubiquitinates and stabilizes the AR resulting in increased transcriptional and proproliferative activity. Conclusion:We have identified Usp12 to be a novel positive regulator of AR. Significance: Usp12 presents a therapeutic target upstream of AR that could enable bypassing the limitations of therapeutics aimed specifically at AR.

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Regulation of the androgen receptor by post-translational modifications

Cited by 121 publications

References 142 publications

Androgens and androgen receptor signaling in prostate tumorigenesis

Androgens and androgen receptor signaling in prostate tumorigenesis

Evidence of androgen action in endometrial and ovarian cancers

Deubiquitinating Enzyme Usp12 Is a Novel Co-activator of the Androgen Receptor

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