A 629RKLKK633 Motif in the Hinge Region Controls the Androgen Receptor at Multiple Levels

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2010 Feb 27

PMID 20186458

Citations 25

Authors

Tamzin M Tanner

Sarah Denayer

Bart Geverts

Nora Van Tilborgh

Stefanie Kerkhofs

Christine Helsen

Lien Spans

Vanessa Dubois

Adriaan B Houtsmuller

Frank Claessens

Annemie Haelens

Affiliations

Soon will be listed here.

Abstract

The androgen receptor protein has specific domains involved in DNA binding, ligand binding, and transactivation, whose activities need to be integrated during transcription activation. The hinge region, more particular a (629)RKLKK(633) motif, seems to play a crucial role in this process. Indeed, although the motif is not part of the DNA-binding domain, its positive residues are involved in optimal DNA binding and nuclear translocation as shown by mutation analysis. When the mutated ARs are forced into the nucleus, however, the residues seem to play different roles in transactivation. Moreover, we show by FRAP analysis that during activation, the AR is distributed in the nucleus in a mobile and two immobile fractions, and that mutations in the (629)RKLKK(633) motif affect the distribution of the AR over these three intranuclear fractions. Taken together, the (629)RKLKK(633) motif is a multifunctional motif that integrates nuclear localization, receptor stability, DNA binding, transactivation potential and intranuclear mobility.

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