The Tumor Suppressors p33ING1 and p33ING2 Interact with Alien in Vivo and Enhance Alien-Mediated Gene Silencing

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• 作者：Inga Fegers ; Robert Kob ; Maren Eckey ; Oliver Schmidt ; Frauke Goeman ; Maria Papaioannou ; Niko Escher ; Ferdinand von Eggeling ; Christian Melle ; Aria Baniahmad
• 刊名：Journal of Proteome Research
• 出版年：2007
• 出版时间：November 2007
• 年：2007
• 卷：6
• 期：11
• 页码：4182 - 4188
• 全文大小：456K
• 年卷期：v.6,no.11(November 2007)
• ISSN：1535-3907

文摘

The tumor suppressor p33ING1 is involved in DNA repair and cell cycle regulation. Furthermore,p33ING1 is a transcriptional silencer that recognizes the histone mark for trimethylated lysine 4 at histoneH3. Interestingly, expression of p33ING1 and p33ING2 is able to induce premature senescence in primaryhuman fibroblasts. The corepressor Alien is involved in gene silencing mediated by selected membersof nuclear hormone receptors. In addition, Alien acts as a corepressor for E2F1, a member of the E2Fcell cycle regulatory family. Furthermore, recent findings suggest that Alien is complexed withtranscription factors participating in DNA repair and chromatin. Here, using a proteomic approach bysurface-enhanced laser desorption ionization and mass spectrometry (SELDI-MS) combined withimmunological techniques, we show that Alien interacts in vivo with the tumor suppressor p33ING1as well as with the related tumor suppressor candidate p33ING2. The interaction of Alien with p33ING1and p33ING2 was confirmed in vitro with GST-pull-down, suggesting a direct binding of Alien to thesefactors. The binding domain was mapped to a central region of Alien. Functionally, the expression ofp33ING1 or p33ING2 enhances the Alien-mediated silencing, suggesting that the interaction plays arole in transcriptional regulation. Thus, the findings suggest that the identified interaction betweenAlien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network.