TY - JOUR
T1 - Protein methyltransferase 2 inhibits NF-κB function and promotes apoptosis
AU - Ganesh, Lakshmanan
AU - Yoshimoto, Takanobu
AU - Moorthy, Narayani C.
AU - Akahata, Wataru
AU - Boehm, Manfred
AU - Nabel, Elizabeth G.
AU - Nabel, Gary J.
PY - 2006/5
Y1 - 2006/5
N2 - The protein arginine methyltransferases (PRMTs) include a family of proteins with related putative methyltransferase domains that modify chromatin and regulate cellular transcription. Although some family members, PRMT1 and PRMT4, have been implicated in transcriptional modulation or intracellular signaling, the roles of other PRMTs in diverse cellular processes have not been fully established. Here, we report that PRMT2 inhibits NF-κB-dependent transcription and promotes apoptosis. PRMT2 exerted this effect by blocking nuclear export of IκB-α through a leptomycin-sensitive pathway, increasing nuclear IκB-α and decreasing NF-κB DNA binding. The highly conserved S-adenosylmethionine-binding domain of PRMT2 mediated this effect. PRMT2 also rendered cells susceptible to apoptosis by cytokines or cytotoxic drugs, likely due to its effects on NF-κB. Mouse embryo fibroblasts from PRMT2 genetic knockouts showed elevated NF-κB activity and decreased susceptibility to apoptosis compared to wild-type or complemented cells. Taken together, these data suggest that PRMT2 inhibits cell activation and promotes programmed cell death through this NF-κB-dependent mechanism.
AB - The protein arginine methyltransferases (PRMTs) include a family of proteins with related putative methyltransferase domains that modify chromatin and regulate cellular transcription. Although some family members, PRMT1 and PRMT4, have been implicated in transcriptional modulation or intracellular signaling, the roles of other PRMTs in diverse cellular processes have not been fully established. Here, we report that PRMT2 inhibits NF-κB-dependent transcription and promotes apoptosis. PRMT2 exerted this effect by blocking nuclear export of IκB-α through a leptomycin-sensitive pathway, increasing nuclear IκB-α and decreasing NF-κB DNA binding. The highly conserved S-adenosylmethionine-binding domain of PRMT2 mediated this effect. PRMT2 also rendered cells susceptible to apoptosis by cytokines or cytotoxic drugs, likely due to its effects on NF-κB. Mouse embryo fibroblasts from PRMT2 genetic knockouts showed elevated NF-κB activity and decreased susceptibility to apoptosis compared to wild-type or complemented cells. Taken together, these data suggest that PRMT2 inhibits cell activation and promotes programmed cell death through this NF-κB-dependent mechanism.
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U2 - 10.1128/MCB.26.10.3864-3874.2006
DO - 10.1128/MCB.26.10.3864-3874.2006
M3 - Article
C2 - 16648481
AN - SCOPUS:33646580357
SN - 0270-7306
VL - 26
SP - 3864
EP - 3874
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 10
ER -