TY - JOUR
T1 - PRMT1 negatively regulates activation-induced cell death in macrophages by arginine methylation of GAPDH
AU - Cho, Jun Ho
AU - Lee, Rana
AU - Kim, Eunju
AU - Choi, Yea Eun
AU - Choi, Eui Ju
N1 - Funding Information:
This work was supported by the National Research Foundation grant ( NRF-2017R1A2B2008193 ) and by the BRL grant ( NRF-2015R1A4A1041919 ) funded by the Ministry of Science and ICT of Korea, and by a Korea University grant (E.-J.C.).
Funding Information:
This work was supported by the National Research Foundation grant (NRF-2017R1A2B2008193) and by the BRL grant (NRF-2015R1A4A1041919) funded by the Ministry of Science and ICT of Korea, and by a Korea University grant (E.-J.C.).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is implicated in cell death in addition to a role as a glycolytic enzyme. In particular, when cells are exposed to cellular stressors involving nitric oxide (NO) production, GAPDH can undergo NO-induced S-nitrosylation and S-nitrosylated GAPDH has been shown to elicit apoptosis. However, the mechanism underlying the regulation of the pro-apoptotic function of GAPDH remains unclear. Here, we found that protein arginine methyltransferase 1 (PRMT1) mediated arginine methylation of GAPDH in primary bone marrow-derived macrophages in a NO-dependent manner. Moreover, PRMT1 inhibited S-nitrosylation of GAPDH as well as its binding to SIAH1, thereby reducing the nuclear translocation of GAPDH in lipopolysaccharide (LPS)/interferon (IFN)-γ-activated macrophages. Furthermore, depletion of PRMT1 expression by RNA interference potentiated LPS/IFN-γ-induced apoptosis in macrophages. Taken together, our results suggest that PRMT1 has a previously unrecognized function to inhibit activation-induced cell death of macrophages through arginine methylation of GAPDH.
AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is implicated in cell death in addition to a role as a glycolytic enzyme. In particular, when cells are exposed to cellular stressors involving nitric oxide (NO) production, GAPDH can undergo NO-induced S-nitrosylation and S-nitrosylated GAPDH has been shown to elicit apoptosis. However, the mechanism underlying the regulation of the pro-apoptotic function of GAPDH remains unclear. Here, we found that protein arginine methyltransferase 1 (PRMT1) mediated arginine methylation of GAPDH in primary bone marrow-derived macrophages in a NO-dependent manner. Moreover, PRMT1 inhibited S-nitrosylation of GAPDH as well as its binding to SIAH1, thereby reducing the nuclear translocation of GAPDH in lipopolysaccharide (LPS)/interferon (IFN)-γ-activated macrophages. Furthermore, depletion of PRMT1 expression by RNA interference potentiated LPS/IFN-γ-induced apoptosis in macrophages. Taken together, our results suggest that PRMT1 has a previously unrecognized function to inhibit activation-induced cell death of macrophages through arginine methylation of GAPDH.
KW - Arginine methylation/GAPDH/ macrophage/nitric oxide/PRMT1
UR - http://www.scopus.com/inward/record.url?scp=85045877391&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2018.04.012
DO - 10.1016/j.yexcr.2018.04.012
M3 - Article
C2 - 29665354
AN - SCOPUS:85045877391
VL - 368
SP - 50
EP - 58
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -