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2012 ; 1820
(6
): 701-11
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S-nitrosylation in the regulation of gene transcription
#MMPMID21640163
Sha Y
; Marshall HE
Biochim Biophys Acta
2012[Jun]; 1820
(6
): 701-11
PMID21640163
show ga
BACKGROUND: Post-translational modification of proteins by S-nitrosylation serves
as a major mode of signaling in mammalian cells and a growing body of evidence
has shown that transcription factors and their activating pathways are primary
targets. S-nitrosylation directly modifies a number of transcription factors,
including NF-?B, HIF-1, and AP-1. In addition, S-nitrosylation can indirectly
regulate gene transcription by modulating other cell signaling pathways, in
particular JNK kinase and ras. SCOPE OF REVIEW: The evolution of S-nitrosylation
as a signaling mechanism in the regulation of gene transcription, physiological
advantages of protein S-nitrosylation in the control of gene transcription, and
discussion of the many transcriptional proteins modulated by S-nitrosylation is
summarized. MAJOR CONCLUSIONS: S-nitrosylation plays a crucial role in the
control of mammalian gene transcription with numerous transcription factors
regulated by this modification. Many of these proteins serve as immunomodulators,
and inducible nitric oxide synthase (iNOS) is regarded as a principal mediatiator
of NO-dependent S-nitrosylation. However, additional targets within the nucleus
(e.g. histone deacetylases) and alternative mechanisms of S-nitrosylation (e.g.
GAPDH-mediated trans-nitrosylation) are thought to play a role in NOS-dependent
transcriptional regulation. GENERAL SIGNIFICANCE: Derangement of SNO-regulated
gene transcription is an important factor in a variety of pathological conditions
including neoplasia and sepsis. A better understanding of protein S-nitrosylation
as it relates to gene transcription and the physiological mechanisms behind this
process is likely to lead to novel therapies for these disorders. This article is
part of a Special Issue entitled Regulation of Cellular Processes by
S-nitrosylation.
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