Glyceraldehyde-3-phosphate dehydrogenase regulates activation of c-Jun N-terminal kinase under oxidative stress.
In: Biochemical & Biophysical Research Communications, Jg. 657 (2023-05-21), S. 1-7
Online
academicJournal
Zugriff:
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acts as a sensor under oxidative stress, leading to induction of various biological responses. Given that mitogen-activated protein kinase (MAPK) signaling pathways mediate cellular responses to a wide variety of stimuli, including oxidative stress, here, we aimed to elucidate whether a cross-talk cascade between GAPDH and MAPKs occurs under oxidative stress. Of the three typical MAPKs investigated—extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase (JNK)—we found that hydrogen peroxide (H 2 O 2)-induced JNK activation is significantly reduced in HEK293 cells treated with small-interfering (si)RNA targeting GAPDH. Co-immunoprecipitation with a GAPDH antibody further revealed protein–protein interactions between GAPDH and JNK in H 2 O 2 -stmulated cells. Notably, both JNK activation and these interactions depend on oxidation of the active-site cysteine (Cys152) in GAPDH, as demonstrated by rescue experiments with either exogenous wild-type GAPDH or the cysteine-substituted mutant (C152A) in endogenous GAPDH -knockdown HEK293 cells. Moreover, H 2 O 2 -induced translocation of Bcl-2-associated X protein (Bax) into mitochondria, which occurs downstream of JNK activation, is attenuated by endogenous GAPDH knockdown in HEK293 cells. These results suggest a novel role for GAPDH in the JNK signaling pathway under oxidative stress. • GAPDH is involved in H 2 O 2 -induced JNK activation. • GAPDH Cys152 plays a critical role in JNK activation via protein–protein interactions. • GAPDH induces Bax mitochondrial translocation following JNK activation. • Our findings uncover an additional non-glycolytic function for GAPDH. [ABSTRACT FROM AUTHOR]
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Glyceraldehyde-3-phosphate dehydrogenase regulates activation of c-Jun N-terminal kinase under oxidative stress.
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Autor/in / Beteiligte Person: | Itakura, Masanori ; Kubo, Takeya ; Kaneshige, Akihiro ; Nakajima, Hidemitsu |
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Zeitschrift: | Biochemical & Biophysical Research Communications, Jg. 657 (2023-05-21), S. 1-7 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 0006-291X (print) |
DOI: | 10.1016/j.bbrc.2023.03.044 |
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