Polyisoprenylated methylated protein methyl esterase (PMPMEase)

Polyisoprenylated methylated protein methyl esterase (PMPMEase) is a specialized serine hydrolase that plays a pivotal role in the post-translational processing of prenylated proteins, including members of the Ras, Rho, and Rab GTPase families (Olowokere et al., 2014). These proteins require a series of modifications—prenylation, proteolysis, and C-terminal methylation—to achieve proper membrane localization and biological activity (Adekeye et al., 2017). PMPMEase specifically catalyzes the hydrolysis of the C-terminal methyl ester, thereby reversing the methylation step and regulating the membrane affinity and signaling capacity of these GTPases (PubMed: 24513104). In various malignancies, such as lung, prostate, and breast cancers, PMPMEase is frequently overexpressed, which contributes to aberrant cell proliferation, survival, and migration (Olowokere et al., 2014). By modulating the methylation status of oncogenic proteins like Ras, PMPMEase serves as a critical regulatory node in signal transduction pathways. Consequently, it has become an attractive target for therapeutic intervention, with small-molecule inhibitors like L-28 demonstrating the ability to disrupt cancer cell growth by interfering with the functional localization of prenylated signaling molecules (Adekeye et al., 2017).

Other names

Prenylated methylated protein methyl esterasePMPM esteraseCarboxylesterase 1 (CES1)Isoprenylated protein methyl esterase

Inhibition of PMPMEase prevents the hydrolysis of the C-terminal methyl ester of prenylated proteins, disrupting their normal cycling and membrane localization, which leads to the suppression of oncogenic signaling pathways like Ras/MAPK (Adekeye et al., 2017).