@article {GANAPATHY-KANNIAPPAN4909, author = {SHANMUGASUNDARAM GANAPATHY-KANNIAPPAN and JEAN-FRANCOIS H. GESCHWIND and RANI KUNJITHAPATHAM and MANON BUIJS and JOSEPHINA A. VOSSEN and IRINA TCHERNYSHYOV and ROBERT N. COLE and LABIQ H. SYED and PRAMOD P. RAO and SHINICHI OTA and MUSTAFA VALI}, title = {Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Is Pyruvylated during 3-Bromopyruvate Mediated Cancer Cell Death}, volume = {29}, number = {12}, pages = {4909--4918}, year = {2009}, publisher = {International Institute of Anticancer Research}, abstract = {Background: The pyruvic acid analog 3-bromopyruvate (3BrPA) is an alkylating agent known to induce cancer cell death by blocking glycolysis. The anti-glycolytic effect of 3BrPA is considered to be the inactivation of glycolytic enzymes. Yet, there is a lack of experimental documentation on the direct interaction of 3BrPA with any of the suggested targets during its anticancer effect. Methods and Results: In the current study, using radiolabeled (14C) 3BrPA in multiple cancer cell lines, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as the primary intracellular target of 3BrPA, based on two-dimensional (2D) gel electrophoretic autoradiography, mass spectrometry and immunoprecipitation. Furthermore, in vitro enzyme kinetic studies established that 3BrPA has marked affinity to GAPDH. Finally, Annexin V staining and active caspase-3 immunoblotting demonstrated that apoptosis was induced by 3BrPA. Conclusion: GAPDH pyruvylation by 3BrPA affects its enzymatic function and is the primary intracellular target in 3BrPA mediated cancer cell death.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/29/12/4909}, eprint = {https://ar.iiarjournals.org/content/29/12/4909.full.pdf}, journal = {Anticancer Research} }