Structural determinants outside of the leucine zipper influence the interactions of CREB and ATF-2: interaction of CREB with ATF-2 blocks E1a-ATF-2 complex formation
| Autor: | H A, Abdel-Hafiz, C Y, Chen, T, Marcell, D J, Kroll, J P, Hoeffler |
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| Rok vydání: | 1993 |
| Předmět: |
Transcriptional Activation
Leucine Zippers Base Sequence Protein Conformation Proto-Oncogene Proteins c-jun Molecular Sequence Data Blood Proteins DNA Activating Transcription Factors Zinc Mutation Humans Adenovirus E1A Proteins Cyclic AMP Response Element-Binding Protein Proto-Oncogene Proteins c-fos HeLa Cells Transcription Factors |
| Zdroj: | Oncogene. 8(5) |
| ISSN: | 0950-9232 |
| Popis: | Dimerization of leucine zipper-containing proteins has been associated characteristically with the formation of a coiled-coil structure between two compatible leucine zipper motifs. In the present study we demonstrate the association of the leucine zipper of cAMP response element-binding protein (CREB) with a zinc finger motif of ATF-2. The association of the CREB leucine zipper with the ATF-2 zinc finger is stabilized if the ATF-2 leucine zipper is intact, implying that the preferred interactive structure of ATF-2 juxtaposes the amino-terminal zinc finger motif of this protein with the carboxy-terminal leucine zipper of this same protein. Furthermore, we demonstrate that the association of the CREB leucine zipper with the ATF-2 zinc finger in vitro blocks the association of the adenoviral E1a protein with ATF-2. Similarly, overexpression of full-length CREB, or a truncated version of this protein corresponding to the carboxy-terminal 74 amino acids that make up the DNA-binding and dimerization domains, can block the ATF-2-mediated transcriptional stimulation by E1a in vivo. Mutation of the ATF-2 zinc finger motif stimulates DNA binding of this protein, and abolishes interactions with E1a and CREB proteins. These results demonstrate that the structural conformation of ATF-2 is critical for DNA binding and protein-protein interactions and, further, that leucine zippers can mediate protein-protein interactions with structural motifs other than leucine zippers. |
| Databáze: | OpenAIRE |
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