The cAMP-responsive element (CRE) modulator protein CREMα has been proposed to be a negative regulator of the CRE-binding protein (CREB). Precisely how CREMα inhibits CREB function is unclear, however, CREMα and CREB have highly related structures, and both proteins bind to consensus CRE sequences with similar affinities. Furthermore, both proteins can be phosphorylated by cAMP-dependent protein kinase A (PKA). Two models have been proposed to explain how CREMα could prevent the activation of genes by PKA- phosphorylated CREB: inhibitory CREMα homodimers could prevent occupancy of the CRE by CREB, or CREMα could block gene activation by forming nonfunctional CREB·CREMα heterodimers. To determine whether CREB·CREMα heterodimers are indeed nonfunctional, we engineered the leucine zipper regions of the two proteins to direct the pattern of dimerization. We then tested the biological activities of the phosphorylated and nonphosphorylated complexes in in vivo transcription assays. Our results indicate that CREMα can contribute to PKA-mediated gene activation when selectively heterodimerized with CREB. Furthermore, this transcriptional activity depends upon the ability of the complexes to be phosphorylated by PKA.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - Nov 18 1994|
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