Role of cyclic GMP in gene regulation

Abstract

Cyclic GMP is produced in response to nitric oxide and natriuretic peptides; cGMP is a key regulator of cell proliferation, differentiation, and apoptosis, and plays an important role in many (patho)physiological processes such as synaptic plasticity, angiogenesis, inflammation, and cardiac hypertrophy. The regulation of gene expression by cGMP has been recognized relatively recently, but cGMP-mediated increases or decreases in the mRNA expression of >60 different genes have been described, and gene expression profiling is just beginning to contribute to the growing list of cGMP-regulated genes. Deletion or over-expression experiments in mice involving components of the cGMP signaling pathway have contributed to our understanding of long-term effects of altered cGMP signaling, including the regulation of gene expression. We will discuss transcriptional and post-transcriptional mechanisms of gene regulation by cGMP, and review specific transcription factors and RNA binding proteins targeted by cGMP. Some of the effects of cGMP on gene expression are indirect, through cGMP modulation of other signaling pathways, e. g. mitogen-activated protein kinase pathways. However, some effects of cGMP can be directly attributed to cGMP regulation of specific transcription factors such as CREB, TFII-I or c-Fos, and are mediated by cGMP-dependent protein kinases. We will discuss specific genes regulated by cGMP in the context of their contribution to particular (patho)physiologic processes regulated by cGMP.