Leucine carboxyl methyltransferase 1 (LCMT1)

Leucine carboxyl methyltransferase 1 (LCMT1) is an enzyme critical for the methylation of the C-terminal leucine residue (Leu309) of the catalytic subunits of several phosphatases, most prominently protein phosphatase 2A (PP2A), as well as PP4 and PP6[2][5][6][8]. This methylation is essential for proper holoenzyme assembly, influences substrate specificity, and is tightly regulated[3][6][7]. LCMT1 uses S-adenosyl methionine (SAM) as a methyl donor[1][3], and its activity governs cellular processes including cell signaling, cell cycle progression, and survival. Loss of LCMT1 is linked to cancer progression, especially in prostate cancer where it affects androgen receptor signaling and resistance to anti-androgen therapy[5]. LCMT1 is structurally a SAM-dependent methyltransferase with unique domains enabling substrate selectivity and tight functional regulation with phosphatase partners[3][4].

Other names

LCMT1LCMTCGI-68PPMT1Protein-leucine O-methyltransferaseProtein phosphatase methyltransferase 1[Phosphatase 2A protein]-leucine-carboxy methyltransferase 1

Inhibition of methyltransferase activity (for experimental inhibitors[1]); Disruption of PP2A holoenzyme assembly via loss of methylation