Linked Life Data

21730049

Source:http://linkedlifedata.com/resource/pubmed/id/21730049

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2011-8-22
pubmed:abstractText
Male sex development and growth occur in response to high affinity androgen binding to the androgen receptor (AR). In contrast to complete amino acid sequence conservation in the AR DNA and ligand binding domains among mammals, a primate-specific difference in the AR NH(2)-terminal region that regulates the NH(2)- and carboxyl-terminal (N/C) interaction enables direct binding to melanoma antigen-A11 (MAGE-11), an AR coregulator that is also primate-specific. Human, mouse, and rat AR share the same NH(2)-terminal (23)FQNLF(27) sequence that mediates the androgen-dependent N/C interaction. However, the mouse and rat AR FXXLF motif is flanked by Ala(33) that evolved to Val(33) in primates. Human AR Val(33) was required to interact directly with MAGE-11 and for the inhibitory effect of the AR N/C interaction on activation function 2 that was relieved by MAGE-11. The functional importance of MAGE-11 was indicated by decreased human AR regulation of an androgen-dependent endogenous gene using lentivirus short hairpin RNAs and by the greater transcriptional strength of human compared with mouse AR. MAGE-11 increased progesterone and glucocorticoid receptor activity independently of binding an FXXLF motif by interacting with p300 and p160 coactivators. We conclude that the coevolution of the AR NH(2)-terminal sequence and MAGE-11 expression among primates provides increased regulatory control over activation domain dominance. Primate-specific expression of MAGE-11 results in greater steroid receptor transcriptional activity through direct interactions with the human AR FXXLF motif region and indirectly through steroid receptor-associated p300 and p160 coactivators.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29951-63
pubmed:dateRevised
2011-10-19
pubmed:meshHeading
pubmed-meshheading:21730049-Amino Acid Motifs, pubmed-meshheading:21730049-Amino Acid Sequence, pubmed-meshheading:21730049-Animals, pubmed-meshheading:21730049-Antigens, Neoplasm, pubmed-meshheading:21730049-COS Cells, pubmed-meshheading:21730049-Cercopithecus aethiops, pubmed-meshheading:21730049-Evolution, Molecular, pubmed-meshheading:21730049-Gene Expression Regulation, pubmed-meshheading:21730049-HeLa Cells, pubmed-meshheading:21730049-Humans, pubmed-meshheading:21730049-Male, pubmed-meshheading:21730049-Mice, pubmed-meshheading:21730049-Neoplasm Proteins, pubmed-meshheading:21730049-Protein Structure, Tertiary, pubmed-meshheading:21730049-Rats, pubmed-meshheading:21730049-Receptors, Androgen, pubmed-meshheading:21730049-Species Specificity, pubmed-meshheading:21730049-Transcription, Genetic, pubmed-meshheading:21730049-p300-CBP Transcription Factors
pubmed:year
2011
pubmed:articleTitle
Gain in transcriptional activity by primate-specific coevolution of melanoma antigen-A11 and its interaction site in androgen receptor.
pubmed:affiliation
Laboratories for Reproductive Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7500, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural