Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis

摘要: Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive often display robust regulation of molecular features modify biological response, which can facilitate identification relevant pathways/networks. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who a pronounced tumorigenic response radiation, in comparison normal human (NHDFs). Our approach exploits newly developed thiol-reactive probes with flexible click chemistry functional group define changes protein thiol profiles live cell studies, minimizes artifacts associated lysis. We observe qualitative differences by SDS-PAGE analysis when detection iodoacetamide vs maleimide probe chemistries compared, and pretreatment cells hydrogen peroxide eliminates the majority bands. Redox revealed deficient expression an apparent 55 kDa GDFs independent donors, compared NHDFs. Proteomics tentatively identified this as aldehyde dehydrogenase 1A1 (ALDH1A1), key enzyme regulating retinoic acid synthesis, deficiency was confirmed Western blot. additional between NHDFs, including responsive annexin family members. results indicate multifactorial basis for unusual sensitivitymore » carcinogenesis, pathways plausible implications health effects.« less