Seminar by Prof. Xavier Salvatella

ICREA and IRB Barcelona (Spain)

Structural basis of aberrant androgen receptor activation in late stage prostate cancer

The nuclear hormone receptor androgen receptor (AR) is a transcription factor of 919 amino acids activated by androgens that regulates the development of the male sexual phenotype. It is composed of three domains: a flexible N-terminal intrinsically disordered transactivation domain that interacts with the transcription machinery, a DNA-binding domain that binds specific DNA sequences adjacent to genes regulated by AR and a C-terminal domain that upon androgen binding undergoes a structural change that activates the protein. To understand the structural basis of transcription activation by the N-terminal domain of AR we have characterized its interaction with general transcription factors that are associated with RNA polymerase and are therefore considered part of the transcription machinery. Our results provide information about the mechanism by which AR activates transcription in castration resistant prostate cancer, a late stage of the disease for which there currently is no treatment.