Cyclic AMP (cAMP) is a crucial regulatory molecule in eukaryotic gene transcription. It coordinates diverse metabolic processes, including glycogen breakdown in mammalian liver and enzyme synthesis in E. coli. While significant progress has been made in understanding cAMP's role in prokaryotic gene regulation, much remains unknown about its mechanism in eukaryotes. Recent studies have identified cAMP-responsive elements (CREs) in eukaryotic genes, which are conserved and function as enhancers. These elements are often located within the first 150 bp of the 5'-flanking region of genes and can act as basal or inducible enhancers. CREs are regulated by cAMP through the cAMP-dependent protein kinase, particularly its catalytic subunit (C subunit), which phosphorylates CRE-binding proteins, enhancing transcription. Two main classes of cAMP-regulated genes have been identified: Group 1 genes, which respond rapidly to cAMP (within minutes), and Group 2 genes, which require several hours of treatment. Group 1 genes are cycloheximide-insensitive, suggesting they involve rapid protein modification. In contrast, Group 2 genes require ongoing protein synthesis. The CRE is a key element in cAMP regulation, and its function is supported by studies showing that it can confer cAMP responsiveness to neutral promoters. Another cAMP-responsive element, the AP-2 binding site, has been identified in some genes. It acts as a basal transcription enhancer and is responsive to cAMP and phorbol esters. The AP-2 element is cell-specific and is involved in the regulation of genes such as metallothionein II A and growth hormone. Factors involved in cAMP-regulated gene transcription include CRE-binding proteins and AP-2. These proteins bind to their respective elements and are regulated by cAMP through phosphorylation. The C subunit of cAMP-dependent protein kinase is the main effector in this process. However, the RII subunit of the kinase does not directly bind to DNA and is not a specific DNA-binding protein. A model for cAMP regulation of gene transcription suggests that cAMP activates transcription by modifying the transcriptional activation domains of CRE-binding proteins and AP-2. This modification enhances the interaction between these proteins and other transcription factors, leading to increased gene expression. The model highlights the role of cAMP in modulating the activity of transcription factors already bound to target sequences in the promoter-regulatory region of the gene. This model is supported by experimental evidence showing that cAMP enhances transcription through phosphorylation events. However, the exact mechanisms and the role of various proteins remain to be fully elucidated.Cyclic AMP (cAMP) is a crucial regulatory molecule in eukaryotic gene transcription. It coordinates diverse metabolic processes, including glycogen breakdown in mammalian liver and enzyme synthesis in E. coli. While significant progress has been made in understanding cAMP's role in prokaryotic gene regulation, much remains unknown about its mechanism in eukaryotes. Recent studies have identified cAMP-responsive elements (CREs) in eukaryotic genes, which are conserved and function as enhancers. These elements are often located within the first 150 bp of the 5'-flanking region of genes and can act as basal or inducible enhancers. CREs are regulated by cAMP through the cAMP-dependent protein kinase, particularly its catalytic subunit (C subunit), which phosphorylates CRE-binding proteins, enhancing transcription. Two main classes of cAMP-regulated genes have been identified: Group 1 genes, which respond rapidly to cAMP (within minutes), and Group 2 genes, which require several hours of treatment. Group 1 genes are cycloheximide-insensitive, suggesting they involve rapid protein modification. In contrast, Group 2 genes require ongoing protein synthesis. The CRE is a key element in cAMP regulation, and its function is supported by studies showing that it can confer cAMP responsiveness to neutral promoters. Another cAMP-responsive element, the AP-2 binding site, has been identified in some genes. It acts as a basal transcription enhancer and is responsive to cAMP and phorbol esters. The AP-2 element is cell-specific and is involved in the regulation of genes such as metallothionein II A and growth hormone. Factors involved in cAMP-regulated gene transcription include CRE-binding proteins and AP-2. These proteins bind to their respective elements and are regulated by cAMP through phosphorylation. The C subunit of cAMP-dependent protein kinase is the main effector in this process. However, the RII subunit of the kinase does not directly bind to DNA and is not a specific DNA-binding protein. A model for cAMP regulation of gene transcription suggests that cAMP activates transcription by modifying the transcriptional activation domains of CRE-binding proteins and AP-2. This modification enhances the interaction between these proteins and other transcription factors, leading to increased gene expression. The model highlights the role of cAMP in modulating the activity of transcription factors already bound to target sequences in the promoter-regulatory region of the gene. This model is supported by experimental evidence showing that cAMP enhances transcription through phosphorylation events. However, the exact mechanisms and the role of various proteins remain to be fully elucidated.