Protein methyltransferase 2 inhibits NF-κB function and promotes apoptosis

Lakshmanan Ganesh, Takanobu Yoshimoto, Narayani C. Moorthy, Wataru Akahata, Manfred Boehm, Elizabeth G. Nabel, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3864-3874
Number of pages11
JournalMolecular and Cellular Biology
Volume26
Issue number10
DOIs
StatePublished - May 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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