ABSTRACT
Retinoylation (acylation RA of protein) is another mechanism which RA may act on cells One metabolic for retinoylation the formation of a retinoyl-CoA intermediate and the subsequent transfer and covalent binding of the retinoyl moiety to protein (22) (Figure RA is incorporated into proteins of HL60 cells and of many other cell types (15-18,20,21,23,24). The proteins labeled by RA are cell type-dependent. In addition, the nature of the covalent bond between the retinoyl moiety protein may vary. In HIL60 cells, about 90% of the total bound RA is released treatment that thioester
may indicalle that if retinoyl-CoA is an intermediate, RA binds to protein either by an amide bond (Figure 1 ), analogous to the binding of myristic acid to an N-terminal glycine (Figure 2), or via an 0-ester bond to either tyrosine, threonine, or serine (Figure 1). Additionally, we include in Figure 1 a speculative pathway showing the formation either of an 0-ether or a thioether bond to protein through the intermediate formation of 4-hydroxy-RA. RA is metabolized to 4-hydroxy-RA
a cytochrome jpq50-catalyzed hydroxylation in mammalian cells (25). 4-Hydroxy-RA is further catabolized to which is present at concentrations approaching those of RA in human plasma (26). It is possible that these metabolites as well as 5,6-epoxy-5,6-dihydro-RA, not shown in Figure 1, can form a covalent bond with protein. Another mechanism for RA binding to protein
1 Proposed for modification way for retinoylation is the formation of a intermediate and the subsequent attachment to a protein-cysteine via a thioester bond. Evidence for this pathway has been reported (15,22). The finding that RA is not bound in thioester linkage to cytokeratins (18) raises other possibilities. Ifretinoyl-S-CoA is an intermediate, then an 0-ester or an amide linkage may be formed. If retinoyl-S-CoA is not an intermediate, then an 0-ether or a thioether bond may be formed shown and discussed in the text.
