A 629RKLKK633 motif in the hinge region controls the androgen receptor at multiple levels.
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.
Tanner
Tamzin M
TM
Molecular Endocrinology Laboratory, Department of Molecular Cell Biology, Catholic University of Leuven, Campus Gasthuisberg O&N1, Herestraat 49, Box 901, 3000, Leuven, Belgium.
Denayer
Sarah
S
Geverts
Bart
B
Van Tilborgh
Nora
N
Kerkhofs
Stefanie
S
Helsen
Christine
C
Spans
Lien
L
Dubois
Vanessa
V
Houtsmuller
Adriaan B
AB
Claessens
Frank
F
Haelens
Annemie
A
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015533:Transcriptional Activation
C410798:AR protein, human; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D004247:DNA