PT  - JOURNAL ARTICLE
AU  - SHANMUGASUNDARAM GANAPATHY-KANNIAPPAN
AU  - JEAN-FRANCOIS H. GESCHWIND
AU  - RANI KUNJITHAPATHAM
AU  - MANON BUIJS
AU  - JOSEPHINA A. VOSSEN
AU  - IRINA TCHERNYSHYOV
AU  - ROBERT N. COLE
AU  - LABIQ H. SYED
AU  - PRAMOD P. RAO
AU  - SHINICHI OTA
AU  - MUSTAFA VALI
TI  - Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Is Pyruvylated during 3-Bromopyruvate Mediated Cancer Cell Death
DP  - 2009 Dec 01
TA  - Anticancer Research
PG  - 4909--4918
VI  - 29
IP  - 12
4099  - http://ar.iiarjournals.org/content/29/12/4909.short
4100  - http://ar.iiarjournals.org/content/29/12/4909.full
SO  - Anticancer Res2009 Dec 01; 29
AB  - 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.