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 fou...

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Bibliographic Details
Published in:	Free radical biology & medicine Vol. 30; no. 12; pp. 1365 - 1373
Main Authors:	Lachaise, Fabienne, Martin, Ghislaine, Drougard, Christianne, Perl, Andras, Vuillaume, Monique, Wegnez, Maurice, Sarasin, Alain, Daya-Grosjean, Leela
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 15-06-2001
Subjects:	Acatalasia Blotting, Western Catalase Cell Transformation, Viral Cells, Cultured - radiation effects DNA - radiation effects DNA Damage DNA Repair - genetics Electrophoresis, Gel, Two-Dimensional Enzyme Activation Fibroblasts Fibroblasts - enzymology Fibroblasts - radiation effects Fibroblasts - virology Free radicals Genetic Predisposition to Disease Humans Isoenzymes - metabolism NADP - biosynthesis NADP - physiology Neoplasms, Radiation-Induced - etiology Oxidative Stress Pentose Phosphate Pathway - physiology Phosphorylation Protein Processing, Post-Translational Radiation Tolerance - genetics Repair-deficient syndromes Simian virus 40 - physiology Skin Neoplasms - etiology Transaldolase Transaldolase - metabolism Two-dimensional electrophoresis Ultraviolet Rays - adverse effects Xeroderma Pigmentosum - complications Xeroderma Pigmentosum - enzymology Xeroderma Pigmentosum - genetics Xeroderma Pigmentosum - pathology Free radicals SDS TTD 1,2-D SOD PAGE Two-dimensional electrophoresis IEF NHF Repair-deficient syndromes CHAPS P Transaldolase PPP Catalase PMSF RT-PCR Fibroblasts SV40 XP GSH PAP TAL
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Summary:	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.
ISSN:	0891-5849 1873-4596
DOI:	10.1016/S0891-5849(01)00532-9