Some aspects of nuclear and cytoplasmic ADP-ribosylation. Biological and pharmacological perspectives.

Abstract

Since the discovery of protein phosphorylation by Burnett and Kennedy (1954) protein ADP-ribosylation appears to be the second most important post-translational modification involved in a great variety of cellular processes (see for review Althaus and Richter, 1987; Mandel et al., 1982; Ueda and Hayaishi, 1985). It is noteworthy that the metabolic specificities and biological functions of cells or tissues are often under the control of post-translational modifications and of their effects. Thus it seemed of interest to extend our knowledge on modulation of ADP-ribosylation processes which occur in diverse cell types in biological and pathological conditions. Let us remind that in addition to the nuclear ADPRT (Chambon et al., 1963; Chambon et al., 1966; Doly and Mandel, 1967) mitochondrial (Masmoudi et al., 1988) cytoplasmic (Thomassin et al., 1985) and plasma membrane bound ADP-ribosyl transferases (see for review Althaus and. Richter, 1987) were described. Our interest is focused on three particularly attractive fields: 1) nervous tissue: growth and differentiation; 2) tumoral cell growth and 3) cytoskeleton ADP-ribosylation. In the first part of the present paper we report some aspects of nuclear ADP-ribosylation reaction of two highly differentiated cell types: neurons and astrocytes. The second part concerns nuclear Po1yADPR activity and mRNA of mastocytoma P815 tumoral cells. The possibilities offered by manipulation of ADP-ribosylation reaction in antitumoral therapy will also be briefly evoked. In the third part of the paper we shall summarize some aspects of cytoplasmic ADPRT and cytoskeleton ADPribosylation which appear of an increasing interest in normal and tumoral cell biology.