Transcriptional Synergy between Melanoma Antigen Gene Protein-A11 (MAGE-11) and p300 in Androgen Receptor Signaling
Transcriptional Synergy between Melanoma Antigen Gene Protein-A11 (MAGE-11) and p300 in Androgen Receptor Signaling
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DOI：
10.1074/jbc.m110.120600
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发表时间：
2010-07-09
影响因子：
4.8
通讯作者：
Wilson, Elizabeth M.
中科院分区：
文献类型：
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作者：
Askew, Emily B.;Bai, Suxia;Wilson, Elizabeth M.
雄激素受体(AR)介导的基因调控涉及与包括黑色素瘤抗原基因蛋白-A11(MAGE-11)在内的共调节蛋白的相互作用。为了了解MAGE-11和腺病毒早期蛋白E1a序列相似性的功能意义，我们确定了MAGE-11是否通过与p300(一种强大的和普遍存在的转录调节因子)相互作用而促进AR的转录活性。在这里，我们报道了MAGE-11通过MAGE-11的MXXIF基序(MXXIF189)-M-185与p300的NH2末端区域相互作用，其转录活性取决于MAGE-11的F-box和MAPK的磷酸化。依赖MAGE-11和p300的AR反式激活的增加需要AR和p300的NH2末端区域、p300乙酰转移酶活性以及AR FXXLF基序(23)FQNLF(27)与MAGE-11的相互作用。MAGE-11将AR与p300和p160共激活因子转录中间蛋白2(TIF2)联系起来。TIF2转录激活需要p300NH2末端的FXXLF基序(33F)GSLF(37)。P300的表达增加降低了MAGE-11的泛素化水平，并一过性增加了内源性MAGE-11的水平。在MAGE-11、p300和TIF2复合体中，p300的自动乙酰化和TIF2的乙酰化减少是明显的。研究表明，MAGE-11通过一系列FXXLF相关的相互作用基序将AR和p300的NH2末端结构域连接起来，促进转录协同作用。
Androgen receptor (AR)-mediated gene regulation involves interactions with coregulatory proteins that include the melanoma antigen gene protein-A11 (MAGE-11). To understand the functional significance of sequence similarity between MAGE-11 and the adenovirus early protein E1A, we determined whether MAGE-11 contributes to AR transcriptional activity through an interaction with p300, a potent and ubiquitous transcriptional regulator. Here, we report that MAGE-11 interacts with the NH2-terminal region of p300 through the MAGE-11 MXXIF motif (MXXIF189)-M-185, with transcriptional activity depending on the MAGE-11 F-box and MAPK phosphorylation. The MAGE-11- and p300-dependent increase in AR transactivation required the NH2-terminal regions of AR and p300, p300 acetyltransferase activity, and the AR FXXLF motif (23)FQNLF(27) interaction with MAGE-11. MAGE-11 linked AR to p300 and the p160 coactivator, transcriptional intermediary protein 2 (TIF2). The p300 NH2-terminal FXXLF motif (33F)GSLF(37) was required for transcriptional activation by TIF2. Increased expression of p300 decreased the ubiquitinylation of MAGE-11 and transiently increased endogenous MAGE-11 levels. Auto-acetylation of p300 and decreased acetylation of TIF2 were evident in the MAGE-11, p300, and TIF2 complex. The studies suggest that MAGE-11 links NH2-terminal domains of AR and p300 to promote transcriptional synergy through a cadre of FXXLF-related interacting motifs.