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Human Androgen Receptor Diseases Reveal the in vivo Impact of Transcription Factor SUMOylation
Author(s) -
IñiguezLluhí Jorge A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.193.2
Subject(s) - sumo protein , androgen receptor , transcription factor , biology , receptor , phenotype , prostate cancer , cancer research , transcription (linguistics) , microbiology and biotechnology , mechanism (biology) , bioinformatics , ubiquitin , genetics , cancer , gene , linguistics , philosophy , epistemology
Transcription factors are often the ultimate mediators of signaling systems. They are responsible for converting short term signals triggered by ligand binding or post‐translational modifications into longer term changes in cell phenotype. Pathologic alterations at this level are responsible for the aberrant phenotype of multiple acute and developmental diseases. The reversible conjugation of Small Ubiquitin‐like MOdifier (SUMO) proteins has emerged as a prevalent and versatile mechanism for the regulation of multiple component of the transcriptional machinery. The impact of this mechanism on human diseases however, is still largely unknown. Using the Androgen Receptor as a paradigm and by taking advantage of molecular information derived from human patients, we have been able to examine how SUMOylation regulates this steroid hormone receptor and discovered how alterations in this post‐translational mechanism contribute to the pathophysiology of human male reproductive disorders, prostate cancer and the neurodegenerative disease Spino‐Bulbar Muscular Atrophy or Kennedy disease. The findings clearly demonstrate the in vivo impact of transcription factor SUMOylation and indicate that SUMO based therapeutic approaches may be of clinical use for multiple transcription factor based diseases.