Glyceraldehyde-3-phosphate dehydrogenase regulates cyclooxygenase-2 expression by targeting mRNA stability

The sweet side ofRNAregulation: glyceraldehyde‐3‐phosphate dehydrogenase as a noncanonicalRNA‐binding protein

“…Regardless, as increased ET‐1 levels are associated with many diseases, controlling ET‐1 production via modulation of its mRNA stability offers a promising novel therapeutic strategy . Similarly, siRNA‐mediated knockdown of GAPDH lead to a moderate increase in Cox‐2 mRNA and protein levels after lipopolysaccharide induction, suggesting that GAPDH may destabilize the Cox‐2 mRNA transcript . Native PAGE gel‐shift assays suggested that GAPDH binding to the core ARE of the Cox‐2 mRNA 3′ UTR may be regulated by cellular GSH/GSSG ratios and GAPDH localization, however, the biological consequences of this interaction remain to be determined.…”

Is RNA Binding in the Rossmann Fold Essential for GAPDH Intranuclear Functions?

“…GAPDH-RNA binding alters mRNA stability (Bonafe et al, 2005;Ikeda et al, 2012;Zeng et al, 2014). Several reports suggest that GAPDH binding to RNA may play a role in nucleocytoplasmic transport of RNA (Singh and Green, 1993;Muller et al, 1992;Hamilton et al, 1993).…”

“…NAD + which is a co-factor of GAPDH, bears structural resemblance to AU-Rich Elements (ARE) often found in 3'-UTR regions of mRNA (Seidler, 2013). Affinity of GAPDH to ARE results in GAPDH binding to several mRNA coding for c-myc, CSF-1/2, IFN-γ, IL-2, ET1, AT1R and COX-2 (Nagy and Rigby, 1995;Rodriguez-Pascual et al, 2008;Zhou et al, 2008;Backlund et al, 2009;Ikeda et al, 2012). Importantly, mutagenesis of residues localized at the GAPDH dimer interface impaired binding of GAPDH to ARE within TNF-α mRNA (White et al, 2015).…”

“…Three types of polynucleotide-GAPDH interaction have been described, so far: (i) GAPDH binding to RNA, mostly represented by AU-Rich Elements (ARE) in the 3'-UTR of mRNA (Nagy and Rigby, 1995;Seidler, 2013) (ii) formation of multiprotein-RNA complexes, with GAPDH and RNA being important structural components (Mazurek et al, 1996;Carlile et al, 1998) (iii) GAPDH binding to single-stranded DNA at telomeric sequences near the chromosomal ends (Sundararaj et al, 2004;Demarse et al, 2009). GAPDH-RNA binding affects mRNA stability and template activity (Bonafe et al, 2005;Rodriguez-Pascual et al, 2008;Backlund et al, 2009;Kondo et al, 2011;Ikeda et al, 2012;Zeng et al, 2014). RNA binding activity of GAPDH is attributed to the Rossmann fold which forms NAD + -binding center located at the Nterminus of GAPDH polypeptide (Rossman, 1981).…”

Chemical genetics and its application to moonlighting in glycolytic enzymes

“…(1) Plasminogen receptor in diverse cell types, facilitating conversion into plasmin and fibrinolysis, which is linked to multiple functions: (i) induction of apoptosis, (ii) tumour invasion, (iii) myogenesis, (iv) neuronal survival (via activation of mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase 1/2 (ERK1/2), and (v) degradation of amyloid β-peptide (Aβ) protein, the major component of amyloid plaques [29] (2) Tubulin binding that suggests a role in modulation of the microtubule network [29] (3) Binding partner for Akt2 signalling molecule [30] (4) Stabilization of the mitochondrial membrane [31] (5) Glucose homoeostasis via regulation of PEPCK expression [21] (6) Inhibition of neuregulin-1-dependent cell proliferation [32] (7) Parasite evasion of host immune system and modulation of the haemostatic response [33] (8) Regulatory component of the renal K + channel (ROMK2) [34] (9) Complex with the putative RNase CvfA to regulate nutritional stress, growth phase control and virulence gene expression (Streptococcus pyogenes) [35] GAPDH (1) Regulation of redox post-translational modifications in plants [36] (2) Function as a transferrin receptor [37] (3) Regulatory component of the renal K + channel (ROMK2; along with enolase) [34] (4) Function as macrophage lactoferrin receptor [38] (5) Induction of cancer cell senescence via interaction with the telomerase RNA component [39] (6) Regulation of cyclo-oxygenase-2 (COX-2) expression; regulated via binding to COX-2 mRNA [40] (7) Extracellular form promotes virulence (S. pyogenes) [41] (8) Complex with Akt to increase Bcl-xL expression and block caspase-independent cell-death [42] (9) Adhesion factor for conidial attachment (Penicillium marneffei) [43] (10) Complement C3-binding activity to evade host immunity (Haemonchus contortus) [44] (11) Inhibition of mitochondrial elimination after ischaemia/repurfusion (via phosphorylation by protein kinase Cδ) [45] (12) Ligand for complement C1q protein (Pneumococcus) [46] (13) Complex with ubiquitin-protein ligase SIAH1 to induce the cell death cascade [17] (14) Protection of ribosomal protein RPL13a from proteasomal degradation [47] (15) Complex with glutamate receptor GluR2 to regulate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR)-mediated neuron excitotoxicity [4...…”