Vol. 263, No. 19, Issue of July 5, pp. 9063-9066, 1988 | William J. Roesler, George R. Vandenbark, and Richard W. Hanson
The article reviews the role of cyclic AMP (cAMP) in regulating gene transcription in eukaryotic cells, focusing on the mechanisms and regulatory elements involved. cAMP is a crucial molecule that coordinates various metabolic processes, and its effects are pleiotropic, altering multiple steps in metabolic pathways. While significant progress has been made in understanding cAMP's actions in prokaryotes like E. coli, the induction of gene expression by cAMP in eukaryotes remains less understood. The review highlights the common characteristics of cAMP-regulated genes, such as rapid response to cAMP, short mRNA half-life, and the presence of cAMP-responsive elements (CREs) in their promoter regions.
The authors classify these genes into two groups: Group 1 genes, which are rapidly regulated by cAMP, and Group 2 genes, which show a slower response. They discuss the identification and characterization of CREs, such as the 8-bp palindromic sequence T(G/T)ACGTCA, and the AP-2 binding site, which are involved in cAMP-induced gene transcription. The role of cAMP-dependent protein kinase (PKA) is also explored, particularly the C subunit, which is believed to be the proximal intermediate in the cAMP signaling pathway.
The review proposes a model for cAMP stimulation of gene transcription, suggesting that cAMP affects the activity of transcription factors already bound to target sequences in the promoter region. This model involves multiple levels of control, including the binding of CRE binding proteins and AP-2 to their respective sites, followed by phosphorylation and subsequent interactions with other transcription factors or non-DNA binding proteins, leading to increased gene transcription. The model is speculative but aligns with existing experimental evidence and shares common features with other proposed mechanisms of gene regulation.The article reviews the role of cyclic AMP (cAMP) in regulating gene transcription in eukaryotic cells, focusing on the mechanisms and regulatory elements involved. cAMP is a crucial molecule that coordinates various metabolic processes, and its effects are pleiotropic, altering multiple steps in metabolic pathways. While significant progress has been made in understanding cAMP's actions in prokaryotes like E. coli, the induction of gene expression by cAMP in eukaryotes remains less understood. The review highlights the common characteristics of cAMP-regulated genes, such as rapid response to cAMP, short mRNA half-life, and the presence of cAMP-responsive elements (CREs) in their promoter regions.
The authors classify these genes into two groups: Group 1 genes, which are rapidly regulated by cAMP, and Group 2 genes, which show a slower response. They discuss the identification and characterization of CREs, such as the 8-bp palindromic sequence T(G/T)ACGTCA, and the AP-2 binding site, which are involved in cAMP-induced gene transcription. The role of cAMP-dependent protein kinase (PKA) is also explored, particularly the C subunit, which is believed to be the proximal intermediate in the cAMP signaling pathway.
The review proposes a model for cAMP stimulation of gene transcription, suggesting that cAMP affects the activity of transcription factors already bound to target sequences in the promoter region. This model involves multiple levels of control, including the binding of CRE binding proteins and AP-2 to their respective sites, followed by phosphorylation and subsequent interactions with other transcription factors or non-DNA binding proteins, leading to increased gene transcription. The model is speculative but aligns with existing experimental evidence and shares common features with other proposed mechanisms of gene regulation.