Phosphorylation within the MafA N terminus regulates C-terminal dimerization and DNA binding.

Guo S, Vanderford NL, Stein R
J Biol Chem. 2010 285 (17): 12655-61

PMID: 20208071 · PMCID: PMC2857093 · DOI:10.1074/jbc.M110.105759

Phosphorylation regulates transcription factor activity by influencing dimerization, cellular localization, activation potential, and/or DNA binding. Nevertheless, precisely how this post-translation modification mediates these processes is poorly understood. Here, we examined the role of phosphorylation on the DNA-binding properties of MafA and MafB, closely related transcriptional activators of the basic-leucine zipper (b-Zip) family associated with cell differentiation and oncogenesis. Many common phosphorylation sites were identified by mass spectrometry. However, dephosphorylation only precluded the detection of MafA dimers and consequently dramatically reduced DNA-binding ability. Analysis of MafA/B chimeras revealed that sensitivity to the phosphorylation status of MafA was imparted by sequences spanning the C-terminal dimerization region (amino acids (aa) 279-359), whereas the homologous MafB region (aa 257-323) conveyed phosphorylation-independent DNA binding. Mutational analysis showed that formation of MafA dimers capable of DNA binding required phosphorylation within the distinct N-terminal transactivation domain (aa 1-72) and not the C-terminal b-Zip region. These results demonstrate a novel relationship between the phosphoamino acid-rich transactivation and b-Zip domains in controlling MafA DNA-binding activity.

MeSH Terms (14)

Animals Cell Differentiation DNA HeLa Cells Humans MafB Transcription Factor Maf Transcription Factors, Large Mice Phosphorylation Protein Binding Protein Multimerization Protein Processing, Post-Translational Protein Structure, Tertiary Recombinant Fusion Proteins

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