GAPDH mediates nitrosylation of nuclear proteins

Michael D. Kornberg, Nilkantha Sen, Makoto R. Hara, Krishna R. Juluri, Judy Van K. Nguyen, Adele M. Snowman, Lindsey Law, Lynda D. Hester, Solomon H. Snyder

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

S-nitrosylation of proteins by nitric oxide is a major mode of signalling in cells. S-nitrosylation can mediate the regulation of a range of proteins, including prominent nuclear proteins, such as HDAC2 (ref. 2) and PARP1 (ref. 3). The high reactivity of the nitric oxide group with protein thiols, but the selective nature of nitrosylation within the cell, implies the existence of targeting mechanisms. Specificity of nitric oxide signalling is often achieved by the binding of nitric oxide synthase (NOS) to target proteins, either directly or through scaffolding proteins such as PSD-95 (ref. 5) and CAPON. As the three principal isoforms of NOS-neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) -are primarily non-nuclear, the mechanisms by which nuclear proteins are selectively nitrosylated have been elusive. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is physiologically nitrosylated at its Cys 150 residue. Nitrosylated GAPDH (SNO-GAPDH) binds to Siah1, which possesses a nuclear localization signal, and is transported to the nucleus. Here, we show that SNO-GAPDH physiologically transnitrosylates nuclear proteins, including the deacetylating enzyme sirtuin-1 (SIRT1), histone deacetylase-2 (HDAC2) and DNA-activated protein kinase (DNA-PK). Our findings reveal a novel mechanism for targeted nitrosylation of nuclear proteins and suggest that protein-protein transfer of nitric oxide groups may be a general mechanism in cellular signal transduction.

Original languageEnglish (US)
Pages (from-to)1094-1100
Number of pages7
JournalNature Cell Biology
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2010

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Glyceraldehyde-3-Phosphate Dehydrogenases
Nuclear Proteins
Nitric Oxide
Histone Deacetylase 2
Proteins
Sirtuin 1
DNA-Activated Protein Kinase
Nuclear Localization Signals
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Protein S
Nitric Oxide Synthase Type II
Sulfhydryl Compounds
Nitric Oxide Synthase
Signal Transduction
Protein Isoforms
Enzymes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kornberg, M. D., Sen, N., Hara, M. R., Juluri, K. R., Nguyen, J. V. K., Snowman, A. M., ... Snyder, S. H. (2010). GAPDH mediates nitrosylation of nuclear proteins. Nature Cell Biology, 12(11), 1094-1100. https://doi.org/10.1038/ncb2114

GAPDH mediates nitrosylation of nuclear proteins. / Kornberg, Michael D.; Sen, Nilkantha; Hara, Makoto R.; Juluri, Krishna R.; Nguyen, Judy Van K.; Snowman, Adele M.; Law, Lindsey; Hester, Lynda D.; Snyder, Solomon H.

In: Nature Cell Biology, Vol. 12, No. 11, 01.11.2010, p. 1094-1100.

Research output: Contribution to journalArticle

Kornberg, MD, Sen, N, Hara, MR, Juluri, KR, Nguyen, JVK, Snowman, AM, Law, L, Hester, LD & Snyder, SH 2010, 'GAPDH mediates nitrosylation of nuclear proteins', Nature Cell Biology, vol. 12, no. 11, pp. 1094-1100. https://doi.org/10.1038/ncb2114
Kornberg MD, Sen N, Hara MR, Juluri KR, Nguyen JVK, Snowman AM et al. GAPDH mediates nitrosylation of nuclear proteins. Nature Cell Biology. 2010 Nov 1;12(11):1094-1100. https://doi.org/10.1038/ncb2114
Kornberg, Michael D. ; Sen, Nilkantha ; Hara, Makoto R. ; Juluri, Krishna R. ; Nguyen, Judy Van K. ; Snowman, Adele M. ; Law, Lindsey ; Hester, Lynda D. ; Snyder, Solomon H. / GAPDH mediates nitrosylation of nuclear proteins. In: Nature Cell Biology. 2010 ; Vol. 12, No. 11. pp. 1094-1100.
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