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 associated with a hypersensitivity to ultraviolet radiation. The ultraviolet component of sunlight can initiate and promote the formation of cutaneous tumors as seen in the skin cancer-prone XP patients. Previously, we have found that the low activity of the NADPH-dependent antioxydant enzyme, catalase, which we have observed in XP diploid fibroblasts and SV40-tranformed cells, could be restored by the addition of NADPH. Here we have analyzed transaldolase, which regulates NADPH levels produced by the pentose phosphate pathway in order to examine how it influences the catalase activity regulated in XP and SV40-transformed cells. We find that transaldolase activity is high in XP and SV40-transformed human fibroblasts, whereas transaldolase transcription is unchanged, suggesting that modification of transaldolase activity is due to a posttranslational modification of the protein. Two-dimensional electrophoresis analysis has allowed us to identify a complex set of transaldolase 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 catalase activity in SV40-transformed cells and in fibroblasts from XP patients who have a high predisposition to develop skin cancer.
Lachaise
F
F
EMEX-CNRS ESA 8080, Université Paris XI, Orsay, France. fabienne.lachaise@emex.u-psud.fr
Martin
G
G
Drougard
C
C
Perl
A
A
Vuillaume
M
M
Wegnez
M
M
Sarasin
A
A
Daya-Grosjean
L
L
D020642:Acatalasia; D015153:Blotting, Western; D002472:Cell Transformation, Viral; D002478:Cells, Cultured / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000528:radiation effects* / Q000821:virology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D009249:NADP / Q000096:biosynthesis / Q000502:physiology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011836:Radiation Tolerance / Q000235:genetics*; D013539:Simian virus 40 / Q000502:physiology*; D012878:Skin Neoplasms / Q000209:etiology; D014153:Transaldolase / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
D007527:Isoenzymes; D009249:NADP; D004247:DNA; D014153:Transaldolase