The Hinge Region as a Key Regulatory Element of Androgen Receptor Dimerization, DNA Binding and Transactivation
Abstract
The androgen receptor (AR) binds direct repeats as well as inverted repeats of the 5'-AGAACA-3' core element. This makes this receptor unique in the family of nuclear receptors. The inverted repeats are called canonical AREs, the direct repeats selective AREs. The high affinity binding to the selective AREs involves a carboxyterminal extension (CTE) of the DNA-binding domain (DBD). We are expressing large amounts of AR fragments to clarify the structure of the AR-DBD + CTE bound to these AREs by X-ray diffractions on co-crystals. The latter will be done in collaboration with Dr. Daniel Gewirth (cfr DAMD17-01-1-0050). In addition, the CTE has been reported to be involved in the transactivating properties of the AR. We have determined minimal deletions in the hinge region which result in a stronger activating AR. Surprisingly, these deletions have a strong negative effect on DNA-binding. Moreover, other deletions result in an AR which is less active (compared to wild type AR) on some AREs. A series of point mutations is being finalized and tested for discriminating mutations which affect only the DNA-binding, the potentiation or the repression of transactivation of the AR.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA416797
Entities
People
- Frank A. Claessens