The polyglutamine-expanded androgen receptor has increased DNA binding and reduced transcriptional activity
Expansion of a polyglutamine-encoding trinucleotide CAG repeat in the androgen receptor (AR) to more than 37 repeats is responsible for the X-linked neuromuscular disease spinal and bulbar muscular atrophy (SBMA). Here we evaluated the effect of polyglutamine length on AR function in oocytes. This a...
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Published in | Biochemistry and biophysics reports Vol. 3; pp. 134 - 139 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier
01.09.2015
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Subjects | |
Online Access | Get full text |
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Summary: | Expansion of a polyglutamine-encoding trinucleotide CAG repeat in the androgen receptor (AR) to more than 37 repeats is responsible for the X-linked neuromuscular disease spinal and bulbar muscular atrophy (SBMA). Here we evaluated the effect of polyglutamine length on AR function in
oocytes. This allowed us to correlate the nuclear AR concentration to its capacity for specific DNA binding and transcription activation
. AR variants with polyglutamine tracts containing either 25 or 64 residues were expressed in
oocytes by cytoplasmic injection of the corresponding mRNAs. The intranuclear AR concentration was monitored in isolated nuclei and related to specific DNA binding as well as transcriptional induction from the hormone response element in the mouse mammary tumor virus (MMTV) promoter. The expanded AR with 64 glutamines had increased capacity for specific DNA binding and a reduced capacity for transcriptional induction as related to its DNA binding activity. The possible mechanism behind these polyglutamine-induced alterations in AR function is discussed. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2405-5808 2405-5808 |
DOI: | 10.1016/j.bbrep.2015.07.014 |