Primate-Specific Multi-Functional Androgen Receptor Coregulator and Proto-Oncogene Melanoma Antigen-A11 (MAGE-A11)

Wilson, Elizabeth M.

doi:10.1007/978-3-319-18729-7_8

Cited by 1 publication

(2 citation statements)

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“…A growing number of coregulatory proteins have been described binding to the NTD, of particular note are members of the p160 coactivator family (SRC-1 and -2), the histone acetyltransferase protein CBP and the general transcription factor TFIIF, which all bind to the AR-AF1 domain 28. Also, of note is the “transcriptional hub” protein MAGE-A11, which binds to the FxxLF motif in the AR-NTD, interacts with CBP (p300) and p160 proteins, and represents a potential tissue-selective AR transcriptional coactivator 29. The AR-NTD has also been shown to modulate binding affinity of the AR-DBD although this relies on covalent binding of the two domains 30.…”

Section: The Role Of the Ar-ntd In Receptor Functionmentioning

confidence: 99%

“… 28 Also, of note is the “transcriptional hub” protein MAGE-A11, which binds to the FxxLF motif in the AR-NTD, interacts with CBP (p300) and p160 proteins, and represents a potential tissue-selective AR transcriptional coactivator. 29 The AR-NTD has also been shown to modulate binding affinity of the AR-DBD although this relies on covalent binding of the two domains. 30 It has also been suggested that expression of the NTD may drive androgen independent nuclear localization and suppress nuclear export of the AR in CRPC.…”

Section: The Role Of the Ar-ntd In Receptor Functionmentioning

confidence: 99%

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A sting in the tail: the N-terminal domain of the androgen receptor as a drug target

Monaghan

McEwan

2016

Asian J Androl

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The role of androgen receptor (AR) in the initiation and progression of prostate cancer (PCa) is well established. Competitive inhibition of the AR ligand-binding domain (LBD) has been the staple of antiandrogen therapies employed to combat the disease in recent years. However, their efficacy has often been limited by the emergence of resistance, mediated through point mutations, and receptor truncations. As a result, the prognosis for patients with malignant castrate resistant disease remains poor. The amino-terminal domain (NTD) of the AR has been shown to be critical for AR function. Its modular activation function (AF-1) is important for both gene regulation and participation in protein-protein interactions. However, due to the intrinsically disordered structure of the domain, its potential as a candidate for therapeutic intervention has been dismissed in the past. The recent emergence of the small molecule EPI-001 has provided evidence that AR-NTD can be targeted therapeutically, independent of the LBD. Targeting of AR-NTD has the potential to disrupt multiple intermolecular interactions between AR and its coregulatory binding partners, in addition to intramolecular cross-talk between the domains of the AR. Therapeutics targeting these protein-protein interactions or NTD directly should also have efficacy against emerging AR splice variants which may play a role in PCa progression. This review will discuss the role of intrinsic disorder in AR function and illustrate how emerging therapies might target NTD in PCa.

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Section: The Role Of the Ar-ntd In Receptor Functionmentioning

confidence: 99%