ABSTRACT
PURPOSE: The aim of this study was to estimate a possibility of mycosis fungoides (MF) diagnostics based on protein profiling in blood serum. EXPERIMENTAL DESIGN: We obtained and analysed samples of blood serum from 23 patients with MF, and 29 psoriasis patients and 22 healthy donors as controls. Protein profiling was carried out using SELDI TOF MS SELDI-TOF and also profiling of 27 cytokines with multiplex immunoassay technology was implemented. RESULTS: MS data analysis of sera did not give satisfactory statistical discrimination between the groups. Antibody-based cytokine profiling revealed a number of cytokines with a change in their concentrations in both MF and psoriasis (IL-1Ra, IL-4, G-CSF). The C-X-C motif chemokine 10 (IP-10, CXCL10) cytokine had a significantly increased concentration (p<0,001) in samples from MF patients as compared with the other groups. CONCLUSIONS AND CLINICAL RELEVANCE: IP-10 may be considered as a promising biomarker for the differentiation between MF and other skin conditions.
Subject(s)
Biomarkers/blood , Chemokine CXCL10/blood , Immunoassay/methods , Mycosis Fungoides/diagnosis , Proteome/analysis , Psoriasis/diagnosis , Skin Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Case-Control Studies , Diagnosis, Differential , Female , Granulocyte Colony-Stimulating Factor/blood , Humans , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin-4/blood , Male , Middle Aged , Mycosis Fungoides/blood , Protein Array Analysis , Psoriasis/blood , Skin , Skin Neoplasms/blood , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methodsABSTRACT
BACKGROUND: Termination of translation in eukaryotes is controlled by two interacting polypeptide chain release factors, eRF1 and eRF3. While eRF1 recognizes nonsense codons, eRF3 facilitates polypeptide chain release from the ribosome in a GTP-dependent manner. Besides termination, both release factors have essential, but poorly characterized functions outside of translation. RESULTS: To characterize further the functions of yeast eRF1 and eRF3, a genetic screen for their novel partner proteins was performed. As a result, the genes for gamma (TEF4 and TEF3/CAM1) and alpha (TEF5/EFB1) subunits of the translation elongation factor eEF1B, known to catalyze the exchange of bound GDP for GTP on eEF1A, were revealed. These genes act as dosage suppressors of a synthetic growth defect caused by some mutations in the SUP45 and SUP35 genes encoding eRF1 and eRF3, respectively. Extra copies of TEF5 and TEF3 can also suppress the temperature sensitivity of some sup45 and sup35 mutants and reduce nonsense codon readthrough caused by these omnipotent suppressors. Besides, overproduction of eEF1Balpha reduces nonsense codon readthrough in the strain carrying suppressor tRNA. Such effects were not shown for extra copies of TEF2, which encodes eEF1A, thus indicating that they were not due to eEF1A activation. CONCLUSION: The data obtained demonstrate involvement of the translation elongation factor eEF1B in modulating the functions of translation termination factors and suggest its possible role in GDP for GTP exchange on eRF3.
