Abstract B9: Arm1: A glutamate methyltransferase capable of methyl esterifying PCNA

Abstract

Abstract Recently we reported on a novel post-translational modification (PTM) present on proliferating cell nuclear antigen (PCNA). This PTM (methyl esterification) was found acidic residues, primarily glutamic acids. Interestingly, methyl esterification of glutamic acids in proteins has only been observed in bacteria where a specialized glutamate carboxyl O-methyltransferase, CheR, has been shown to methyl esterify specific glutamic acid residues of receptors during chemotaxis signaling. In eukaryotic cells, however, only three carboxyl O-methyltransferases are known to exist and none of them have specificity for glutamic acid residues. Here we describe the isolation and identification of a protein encoded by an unknown open reading frame and expressed in human cells that may represent the first eukaryotic glutamate carboxyl O-methyltransferase, which can modify PCNA. Sequence alignment of this protein with other protein carboxyl O-methyltransferases has demonstrated the existence of multiple consensus and conserved regions, and secondary structural predictions confirm a potential to form a SAM-dependent methyltransferase fold in its C-terminus. We therefore named this protein acidic residue methyltransferase 1 (Arm1). The biological significance of this discovery and its potential role(s) in DNA replication and repair will be discussed. Citation Information: Cancer Res 2009;69(23 Suppl):B9.