Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

Get Instant Access

Studies in the NR field have identified families of proteins known as coactivators and corepres-sors, which modulate the function of transcription factors.79,80 Coactivators act by binding to the receptor in a ligand-dependent fashion and enhance ligand-dependent gene transcription. Overexpression of these coactivators can enhance the transcription of androgen-responsive genes in vitro. Conversely, downregulation of the corepressors is postulated to achieve the same effect. Many NR coactivators contain one or multiple copies of the a-helical LXXLL signature motif (where L is leucine and X is any amino acid). This motif mediates ligand-dependent coactivator NR or coactivator-coac-tivator interactions. Examples of coactivators known to directly interact with NRs include steroid receptor coactivator-1 (SRC-1), tran-scriptional intermediary factor 2 (TIF2), and amplified in breast cancer-1 (AIB-1). The latter is amplified in breast and ovarian cancers.81 Gregory et al.82 reported higher levels of AR, TIF2 and SRC-1 in recurrent human prostate cancer as well as in the CRW22 xenograft model. The AR-associated protein ARA70 is a prototype AR coactivator whose expression not only activates the transcription of androgen-responsive genes but also alters the ligand specificity of AR such that antagonists function as agonist.83

Two known corepressors of the NR super-family are the NR corepressor (N-CoR) and silencing mediator of retinoic and thyroid hormone receptors. Decreased levels of N-CoR correlate with acquisition of resistance to the ER tamoxifen in a breast cancer xenograft model.84 Evidence on AR corepressors was lacking until a recent report detailing the role of members of the protein inhibitor of activated signal transducer and activator of transcription protein inhibitor of activated STAT (PIAS) family. Four members of the PIAS family have been identified: PIAS1, PIAS3, PIASx, and PIASy. The latter acts as a potent inhibitor of AR transcrip-tional activity.85 In contrast, PIAS1 and PIAS3 act as coactivators. Even more interestingly, PIASy possesses an LXXLL signature motif, which appears to be essential for its transrepression activity. Clearly, our knowledge of the interactions between AR and its coactivators and corepressors is still limited and needs further investigation.

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment