Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis
Nilkantha Sen,Makoto R. Hara,Makoto R. Hara,Michael D. Kornberg,Matthew B. Cascio,Byoung-Il Bae,Neelam Shahani,Bobby Thomas,Ted M. Dawson,Valina L. Dawson,Solomon H. Snyder,Akira Sawa +11 more
Reads0
Chats0
TLDR
It is shown that nuclear GAPDH is acetylated at Lys 160 by the acetyltransferase p300/CREB binding protein (CBP) through direct protein interaction, which in turn stimulates the acetolation and catalytic activity of p 300/CBP.Abstract:
Besides its role in glycolysis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) initiates a cell death cascade. Diverse apoptotic stimuli activate inducible nitric oxide synthase (iNOS) or neuronal NOS (nNOS), with the generated nitric oxide (NO) S-nitrosylating GAPDH, abolishing its catalytic activity and conferring on it the ability to bind to Siah1, an E3-ubiquitin-ligase with a nuclear localization signal (NLS). The GAPDH-Siah1 protein complex, in turn, translocates to the nucleus and mediates cell death; these processes are blocked by procedures that interfere with GAPDH-Siah1 binding. Nuclear events induced by GAPDH to kill cells have been obscure. Here we show that nuclear GAPDH is acetylated at Lys 160 by the acetyltransferase p300/CREB binding protein (CBP) through direct protein interaction, which in turn stimulates the acetylation and catalytic activity of p300/CBP. Consequently, downstream targets of p300/CBP, such as p53 (Refs 10,11,12,13,14,15), are activated and cause cell death. A dominant-negative mutant GAPDH with the substitution of Lys 160 to Arg (GAPDH-K160R) prevents activation of p300/CBP, blocks induction of apoptotic genes and decreases cell death. Our findings reveal a pathway in which NO-induced nuclear GAPDH mediates cell death through p300/CBP.read more
Citations
More filters
Journal ArticleDOI
H2S Signals Through Protein S-Sulfhydration
Asif K. Mustafa,Moataz M. Gadalla,Nilkantha Sen,Seyun Kim,Weitong Mu,Sadia K. Gazi,Roxanne K. Barrow,Guangdong Yang,Rui Wang,Solomon H. Snyder +9 more
TL;DR: Ex vivo endogenous H2S physiologically modifies cysteine residues in many proteins, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and actin, converting Cysteine -SH groups to -SSH groups in a process the authors call S-sulfhydration.
Journal ArticleDOI
Glutamate receptors, neurotoxicity and neurodegeneration
Anthony Lau,Michael Tymianski +1 more
TL;DR: There are currently no pharmacological interventions capable of providing significant neuroprotection in the clinical setting of brain ischaemia or injury, and this review addresses the current state of excitotoxic research.
Journal ArticleDOI
H2S signalling through protein sulfhydration and beyond
Bindu D. Paul,Solomon H. Snyder +1 more
TL;DR: Physiological actions of sulfhydration include the regulation of inflammation and endoplasmic reticulum stress signalling as well as of vascular tension.
Journal ArticleDOI
Protein S-nitrosylation in health and disease: a current perspective
TL;DR: Recent findings that implicate S-nitrosylation in cardiovascular, pulmonary, musculoskeletal and neurological (dys)function, as well as in cancer are reviewed.
Journal ArticleDOI
Multiple roles of HDAC inhibition in neurodegenerative conditions.
TL;DR: The targets and mechanisms underlying improvements in neurological performance, learning/memory and other disease phenotypes, and the potential for some HDAC inhibitors to prove clinically effective in the treatment of neurodegenerative disorders are discussed.
References
More filters
Journal ArticleDOI
Surfing the p53 network
TL;DR: The p53 tumour-suppressor gene integrates numerous signals that control cell life and death, and the disruption of p53 has severe consequences when a highly connected node in the Internet breaks down.
Journal ArticleDOI
The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases
TL;DR: It is demonstrated that p300/CBP acetylates nucleosomes in concert with PCAF, a novel class of acetyltransferases in that it does not have the conserved motif found among various other acetyl transferases.
Journal ArticleDOI
Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
Wei Gu,Robert G. Roeder +1 more
TL;DR: It is demonstrated that p53 can be modified by acetylated both in vivo and in vitro, indicating a novel pathway for p53 activation and providing an example of an acetylation-mediated change in the function of a nonhistone regulatory protein.
Journal ArticleDOI
Protein S-nitrosylation: purview and parameters.
Douglas T. Hess,Akio Matsumoto,Sung Oog Kim,Harvey E. Marshall,Jonathan S. Stamler,Jonathan S. Stamler +5 more
TL;DR: S-nitrosylation conveys a large part of the ubiquitous influence of nitric oxide on cellular signal transduction, and provides a mechanism for redox-based physiological regulation.
Journal ArticleDOI
p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa.
Andreas Villunger,Andreas Villunger,Ewa M. Michalak,Leigh Coultas,Franziska Müllauer,Günther Böck,Michael J. Ausserlechner,Jerry M. Adams,Andreas Strasser +8 more
TL;DR: In mice with either noxa or puma disrupted, decreased DNA damage–induced apoptosis in fibroblasts is observed, although only loss of Puma protected lymphocytes from cell death, and Puma deficiency protected cells against diverse p53-independent cytotoxic insults.