Affinity purification of ARE-binding proteins identifies poly(A)-binding protein 1 as a potential substrate in MK2-induced mRNA stabilization

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• 作者：Bollig ; Frank ; Winzen ; Reinhard ; Gaestel ; Matthias ; Kostka ; Susanne ; Resch ; Klaus ; Holtmann ; Helmut
• 关键词：mRNA stability ; AU-rich element ; Affinity purification ; p38 MAP kinase ; MAPKAP kinase 2 ; RNA-binding protein ; PABP1 ; Cytokines
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2003
• 出版时间：February 14, 2003
• 年：2003
• 卷：301
• 期：3
• 页码：665-670
• 全文大小：199 K

文摘

An important determinant for the expression level of cytokines and proto-oncogenes is the rate of degradation of their mRNAs. AU-rich sequence elements (AREs) in the 3^′ untranslated regions have been found to impose rapid decay of these mRNAs. ARE-containing mRNAs can be stabilized in response to external signals which activate the p38 MAP kinase cascade including the p38 MAP kinase substrate MAPKAP kinase 2 (MK2). In an attempt to identify components downstream of MK2 in this pathway we analyzed several proteins which selectively interact with the ARE of GM-CSF mRNA. One of them, the cytoplasmic poly(A)-binding protein PABP1, co-migrated with a protein that showed prominent phosphorylation by recombinant MK2. Phosphorylation by MK2 was confirmed using PABP1 purified by affinity chromatography on poly(A) RNA. The selective interaction with an ARE-containing RNA and the phosphorylation by MK2 suggest that PABP1 plays a regulatory role in ARE-dependent mRNA decay and its modulation by the p38 MAP kinase cascade.