C-terminal CTII motif of 2',3'-cyclic nucleotide 3'-phosphodiesterase undergoes carboxylmethylation.
Eukaryotic proteins with a carboxyl-terminal CaaX motif are modified by isoprenylation and subsequently processed by proteolysis of the three terminal amino acids and carboxylmethylation of the exposed cysteine residue. The myelination-associated 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) has a C-terminal CTII sequence and is isoprenylated; however, no examples of subsequent processing exist when threonine, a polar residue, is located adjacent to the cysteine. Here we show that CNP is capable of being carboxylmethylated in both insect cells and glioma cells. This processing is dependent upon isoprenylation of the cysteine and can be inhibited with the isoprenylated cysteine derivative, N-acetyl-S-farnesyl-L-cysteine. Although the role of the methyl group at the C-terminus of other isoprenylated proteins is not fully understood, modulation of signal transduction pathways is strongly indicated. This modification of CNP may similarly regulate cell biological processes in myelinogenesis.
Cox
M E
ME
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Gao
E N
EN
Braun
P E
PE
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000737:chemistry / Q000378:metabolism*; D000478:Alkylation; D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002460:Cell Line; D002474:Cell-Free System; D005910:Glioma / Q000473:pathology; D008745:Methylation; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009836:Oligodendroglia / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*; D018411:Spodoptera; D014407:Tumor Cells, Cultured
D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571339:Cnp protein, rat