Accession Number:

ADA416797

Title:

The Hinge Region as a Key Regulatory Element of Androgen Receptor Dimerization, DNA Binding and Transactivation

Descriptive Note:

Final rept. 1 Apr 2002-31 Mar 2003

Corporate Author:

KATHOLIEKE UNIV RESEARCH AND DEVELOPMENT LEUVEN (BELGIUM)

Personal Author(s):

Report Date:

2003-05-01

Pagination or Media Count:

17.0

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.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE