Oligoadenylate and cyclic AMP: interrelation and mutual regulation.
The data obtained are in good agreement with the hypothesis that cAMP is involved in the control of 2-5A metabolism, including the mediation of the regulation of 2-5A by IFNs; 2-5A, in turn, affects the intracellular cAMP level. The general question originating from the data is that of a biochemical mechanism connecting the activation of the cAMP/2-5A system and the effect of depression of cell division. In my opinion, this universal effect is the result of the action of the known 2-5A-dependent mechanism, namely, RNase L (see review by Pestka et al. 1987), rather than by any new 2-5A-stimulating enzyme. The RNase L activated by 2-5A decreases the total level of protein synthesis and accelerates the degradation of cellular RNA, resulting in the inhibition of cell growth. It should be mentioned that such activation of RNA turnover is generally characteristic for nondividing cells, especially for cells in the resting state (Epifanova et al. 1983). Thus, the regulatory system of cAMP/2-5A is involved evidently in the antiproliferative mechanism characteristic for the resting cells, controlling the variations in the levels of RNA turnover and protein synthesis.
Itkes
A V
AV
Institute of Molecular Biology, Academy of Sciences of Russia, Moscow.
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism*; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007372:Interferons / Q000502:physiology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009843:Oligoribonucleotides / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000227:Adenine Nucleotides; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009843:Oligoribonucleotides; D014157:Transcription Factors; C023505:2',5'-oligoadenylate; D007372:Interferons; D000242:Cyclic AMP; D015088:2',5'-Oligoadenylate Synthetase; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases