Exp Mol Med.  1997 Mar;29(1):35-43.

Protein methylation in cellular proliferation and differentiation: Non-histone nuclear methyl acceptor protein(s) during 3'-methyl-4-dimethylaminoazobenzeneinduced hepatocarcinogenesis

• Paik MK
• Han YJ
• Hong JH
• Kim JS
• Suh KS
• Yoon SJ

Abstract

An accelerating effect of methyl-deficient diet (MDD) on hepatocarcinogenesis and methylation pattern of nuclear protein(s) by S-adenosylmethionine: protein arginine N-methyltransferase (protein methylase I, PM-I) have been studied with 3'-methyl-4-dimethyl- aminoazobenzene(MeDAB)-treated rats. The MDD+MeDAB-fed group produced typical cancer cells in the liver almost two weeks earlier than the control synthetic diet (CSD)+MeDAB-fed group. Protein methylase I (PM-I) activity in the livers of MDD alone fed rats began to increase at around 2 weeks after MDD-feeding, reaching a peak at 4 weeks and declining thereafter. When nuclei isolated either from normal livers or from cholangiocarcinoma cells were incubated with PM-I preparation from normal liver, 16 and 23-kDa nuclear proteins were the major methylated proteins, regardless of the source of the nuclei. However, when the above mentioned nuclei were incubated with PM-I preparations either from MDD alone fed livers or MDD+ MeDAB-induced cholangiocarcinoma cells, the methylation of 23-kDa protein was not detected. The result suggests that there is a hitherto-unknown PM-I specific to 23 kDa nuclear protein which was lost during methyl deficient diet feeding and hepatocarcinogenesis. The N-terminal 20 amino acids sequence of the 23-kDa protein was found to be (1)Gly-Val-Pro-Leu-(5)X-Arg-Leu-Phe-Asp-(10)His-Ala-Met-Leu-Gln-(15)Ala -His-Arg-Ala-His-(20)Glu, having 94.7% sequence homology with human chorionic somatomammotropin precursor A and B.

Keyword

protein methyltransferases; cell division; cell differentiation; nuclear proteins; rat; dimethylaminoazobenzene; hepatoma; carcinogens

MeSH Terms

Amino Acids
Animals
Arginine
Carcinogens
Carcinoma, Hepatocellular
Cell Differentiation
Cell Division
Cell Proliferation*
Cholangiocarcinoma
Diet
Food, Formulated
Liver
Methylation*
Nuclear Proteins
p-Dimethylaminoazobenzene
Placental Lactogen
Protein Methyltransferases
Protein-Arginine N-Methyltransferases
Rats
S-Adenosylmethionine
Sequence Homology
Amino Acids
Arginine
Carcinogens
Nuclear Proteins
Placental Lactogen
Protein Methyltransferases
Protein-Arginine N-Methyltransferases
S-Adenosylmethionine
p-Dimethylaminoazobenzene