GAPDH mediates nitrosylation of nuclear proteins
Michael D Kornberg1, Nilkantha Sen, Makoto R Hara
1Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nature Cell Biology
|October 26, 2010
Summary
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transports nitric oxide groups to the nucleus. This nitrosylated GAPDH then modifies nuclear proteins, revealing a new cellular signaling pathway.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Biochemistry
Background:
- Nitric oxide (NO) mediates cellular signaling through protein S-nitrosylation.
- Nuclear protein nitrosylation mechanisms were previously unclear, as nitric oxide synthases (NOS) are mainly non-nuclear.
- Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known to be nitrosylated.
Purpose of the Study:
- To elucidate the mechanism of selective nuclear protein nitrosylation.
- To investigate the role of nitrosylated GAPDH in nuclear signaling.
Main Methods:
- Investigated the interaction between nitrosylated GAPDH (SNO-GAPDH) and nuclear proteins.
- Utilized knowledge of Siah1's nuclear localization signal.
- Examined the transnitrosylation activity of SNO-GAPDH on nuclear targets.
Main Results:
- SNO-GAPDH binds to Siah1 and is transported into the nucleus.
- SNO-GAPDH physiologically transnitrosylates key nuclear proteins, including SIRT1, HDAC2, and DNA-PK.
- Demonstrated protein-protein transfer of nitric oxide groups as a novel signaling mechanism.
Conclusions:
- A novel pathway for targeted nuclear protein nitrosylation mediated by SNO-GAPDH has been identified.
- Protein-protein transfer of nitric oxide groups represents a general mechanism in cellular signal transduction.
- This finding addresses the long-standing question of how nuclear proteins are selectively nitrosylated.
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