Protein carboxyl methylation increases in parallel with differentiation of neuroblastoma cells.
Cells of mouse neuroblastoma clone N1E-115 in the confluent phase of growth can catalyze the formation of endogenous protein carboxyl methyl esters, using a protein carboxyl methylase and membrane-bound methyl acceptor proteins. The enzyme is localized predominantly in the cytosol of the cells and has a molecular weight of about 20,000 daltons. Treatment of the cells with dimethylsulfoxide (DMSO) or hexamethylene-bisacetamide (HMBA), agents that induce morphological and electrophysiological differentiation, results in a marked increase in protein carboxyl methylase activity. Maximal levels are reached 6-7 days after exposure to the agents, a time course that closely parallels the development of electrical excitability mechanisms in these cells. Serum deprivation also causes neurite outgrowth but does not enhance electrical excitability or enzyme activity. The capacity of membrane-bound neuroblastoma protein(s) to be carboxyl methylated is increased by the differentiation procedures that have been examined. However, the increase in methyl acceptor proteins induced by DMSO or HMBA is the largest, and its time course parallels electrophysiological differentiation. In contrast, serum deprivation induced a small increase that reached maximal levels within 24 h. The data suggest that increased protein carboxyl methylation is a developmentally regulated property of neuroblastoma cells and that at least two groups of methyl acceptor proteins are induced during differentiation: a minor group related to morphological differentiation, and a major group that may be related to ionic permeability mechanisms of the excitable membrane.
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002999:Clone Cells; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000503:physiopathology*; D012436:S-Adenosylmethionine / Q000378:metabolism
D009363:Neoplasm Proteins; D012436:S-Adenosylmethionine; D008715:Methionine