ADP-ribosylation of nuclear proteins.

ADP-ribosylation can be defined as the postsynthetic modification of protein by the covalent attachment of the ADP-ribose moiety of NAD+. ADP-ribosylation of elongation-factor Tu is responsible for the inhibition of protein synthesis by both diptheria and Pseudomonas aeroginosa toxins (Hilz & Stone, 1976). The activation of membrane adenylate cyclase by cholera toxin is thought to occur by ADP-ribosylation of the adenylate cyclase-associated GTP binding protein (Gill & Meren, 1978). It has also been proposed as a mechanism by which Escherichia coli RNA polymerase activity is modified during bacteriophage T4 infection (Goff, 1974; Rohrer et al., 1975; Skorko et al., 1977). Coliphage N4 has also been reported to contain an intrinsic ADP-ribosyltransferase activity (Pesce et al., 1976). ADP-ribosyltransferase activity is also present in the mitochondria and nuclei of all eukaryotic organisms examined to date. The field of ADP-ribosylation has been comprehensively reviewed by Sugimura (1973), Hilz & Stone (1976) and Hayaishi & Ueda (1977). The present review is concerned exclusively with ADP-ribosylation carried out in eukaryotic nuclei and will concentrate on the large amount of data that has emerged subsequent to the publication of other reviews. The enzyme responsible for ADP-ribosylation in nuclei is termed poly(ADP-ribose) synthetase or polymerase; the name is derived from the fact that, unlike other ADP-ribosyltransferases, the enzyme is capable of synthesizing a protein-bound homopolymer of ADP-ribose, poly(ADP-ribose) (Chambon et al., 1966; Reeder et al., 1967; Fujimura et al., 1967). NAD is cleaved at the nicotinamide-ribose bond (bond energy 34 kJ/mol) and the ADP-ribose moiety transferred to either a nuclear protein or a protein-bound ADP-ribose molecule. The polymer thus formed is degraded by another nuclear enzyme, poly(ADP-ribose) glycohydrolase, producing the free monomeric form of ADP-ribose (Miwa & Sugimura, 1971) (Fig. 1 ) .