Pathways & interactions
cAMP response element binding (CREB) protein (IPR001630)
Short name: Leuzip_CREB
Overlapping homologous superfamilies
- cAMP response element binding (CREB) protein (IPR001630)
- cAMP-responsive element-binding protein 1 (IPR029802)
- cAMP-responsive element-binding protein 3-like protein 1 (IPR029805)
Transcription initiation is dictated by the presence and activity of specific nuclear factors that bind to DNA regulatory sequences and interact with the transcriptional machinery. The functions of some of these factors can be altered by phosphorylation, which affects both DNA binding and transcriptional activation [PMID: 1847666]. Phosphorylation is effected by specific protein kinases that have been activated by the stimulus of signal transduction pathways, resulting in the regulation of gene transcription by modulating the phosphorylation sites of transcription factors.
Cyclic AMP (cAMP) regulates the expression of many genes via a conserved gene promoter element CRE (cAMP response element) [PMID: 2141384], which has the sequence 5'-TGACGTCA-3' [PMID: 2521922]. The cAMP response element binding protein (CREB) is a nuclear factor that is regulated by protein kinase A phosphorylation. Transcription is stimulated on binding to the CRE of a phosphorylated CREB dimer, which is held together by leucine zippers. Dimerisation and transcriptional efficacy have been found to be stimulated by phosphorylation at several distinct sites, and it has thus been suggested [PMID: 2141384] that CREB may be regulated by multiple kinases. Sequence analysis of the gene has revealed a cluster of protein kinase A, protein kinase C, and casein kinase II consensus recognition sites near the N terminus of the protein sequence, and the proximity of these sites to one another indicates the possibility of interaction in a positive or negative fashion to regulate CREB bioactivity.
The 'leucine zipper' is a structure that is believed to mediate the function of several eukaryotic gene regulatory proteins. The zipper consists of a periodic repetition of leucine residues at every seventh position, and regions containing them appear to span 8 turns of alpha-helix. The leucine side chains that extend from one helix interact with those from a similar helix, hence facilitating dimerisation in the form of a coiled-coil. Leucine zippers are present in many gene regulatory proteins, including the CREB proteins, Jun/AP1 transcription factors, fos oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes, and so on.
- PR00041 (LEUZIPPRCREB)