Heterodimerization is mainly responsible for the dominant negative activity of amino-terminally truncated rat androgen receptor forms.
Rat androgen receptor (rAR) mutants devoid of the amino-terminal transactivation domain are able to behave as dominant negative regulators of wild-type rAR. To address the underlying mechanisms of the trans-dominant negative action, we have examined the roles of the DNA-binding domain (DBD) and the ligand-binding domain (LBD) in this process. Transactivation experiments in CV-1 cells complemented by electrophoretic mobility shift assays revealed that the dominant negative receptor forms repress the function of wild-type rAR mainly through heterodimer formation, rather than through competition for binding to cognate DNA elements. Heterodimerization of receptor forms containing LBDs may take place even in the absence of specific DNA binding.
Ikonen
T
T
Department of Physiology, Institute of Biomedicine, Helsinki, Finland.
Palvimo
J J
JJ
Jänne
O A
OA
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D000882:Haplorhini; D011485:Protein Binding; D051381:Rats; D011944:Receptors, Androgen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D017384:Sequence Deletion; D015533:Transcriptional Activation / Q000502:physiology*; D014444:Tyrosine Transaminase / Q000235:genetics
D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D004247:DNA; D014444:Tyrosine Transaminase