Abstract:
:The androgen receptor (AR) is a ligand-activated transcription factor that interacts with coregulatory proteins during androgen-dependent gene regulation. Melanoma antigen gene protein 11 (MAGE-11) is an AR coregulator that specifically binds the AR NH(2)-terminal FXXLF motif and modulates the AR NH(2)- and carboxyl-terminal N/C interaction to increase AR transcriptional activity. Here we demonstrate that epidermal growth factor (EGF) signaling increases androgen-dependent AR transcriptional activity through the posttranslational modification of MAGE-11. EGF in the presence of dihydrotestosterone stabilizes the AR-MAGE complex through the site-specific phosphorylation of MAGE-11 at Thr-360 and ubiquitinylation at Lys-240 and Lys-245. The time-dependent EGF-induced increase in AR transcriptional activity by MAGE-11 is mediated through AR activation functions 1 and 2 in association with the increased turnover of AR and MAGE-11. The results reveal a dynamic mechanism whereby growth factor signaling increases AR transcriptional activity through the covalent modification of an AR-specific coregulatory protein. Sequence conservation of the MAGE-11 phosphorylation and ubiquitinylation sites throughout the MAGE gene family suggests common regulatory mechanisms for this group of cancer-testis antigens.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Bai S,Wilson EMdoi
10.1128/MCB.01672-07subject
Has Abstractpub_date
2008-03-01 00:00:00pages
1947-63issue
6eissn
0270-7306issn
1098-5549pii
MCB.01672-07journal_volume
28pub_type
杂志文章abstract::Cytosine methylation at CpG dinucleotides is thought to cause more than one-third of all transition mutations responsible for human genetic diseases and cancer. We investigated the methylation status of the CpG dinucleotide at codon 248 in exon 7 of the p53 gene because this codon is a hot spot for inactivating mutati...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.4225
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.4.1746
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.2.657-668.2002
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1971
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1993-06-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.5.1545-1554.2002
更新日期:2002-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.11.5879
更新日期:1995-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2004-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.23.10.3405-3416.2003
更新日期:2003-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.10.8.4007
更新日期:1990-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.19.8611-8626.2004
更新日期:2004-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.4.2366
更新日期:1993-04-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1998-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1992-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2000-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2005-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2004-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00