Relationship between posttranslational modification of transaldolase and catalase deficiency in UV-sensitive repair-deficient Xeroderma Pigmentosum fibroblasts and SV40-transformed human cells

Xeroderma Pigmentosum (XP) is a rare recessively inherited human disease as sociated with a hypersensitivity to ultraviolet radiation. The ultraviolet component of sunlight can initiate and promote the formation of cutaneous t umors as seen in the skin cancer-prone XP patients. Previously, we have fou nd that the low activity of the NADPH-dependent antioxydant enzyme, catalas e, which we have observed in XP diploid fibroblasts and SV40-tranformed cel ls, could be restored by the addition of NADPH. Here we have analyzed trans aldolase, which regulates NADPH levels produced by the pentose phosphate pa thway in order to examine how it influences the catalase activity regulated in XP and SV40-transformed cells. We find that transaldolase activity is h igh in XP and SV40-transformed human fibroblasts, whereas transaldolase tra nscription is unchanged, suggesting that modification of transaldolase acti vity is due to a posttranslational modification of the protein. Two-dimensi onal electrophoresis analysis has allowed us to identify a complex set of t ransaldolase isoforms and to postulate that the phosphorylation of specific isoforms could be correlated with the different enzymatic activities seen. Our results show that high transaldolase activity corresponds to a low cat alase activity in SV40-transformed cells and in fibroblasts from XP patient s who have a high predisposition to develop skin cancer. (C) 2001 Elsevier Science Inc.