Analysis of radiation-inducible hSNK gene in human thyroid cells

The late effect of radiation on thyroid tumorigenesis is closely associated with the disturbance of cell cycle regulation. The polo-like kinase (PLKs) family plays an important role in several stages of mitosis. Using the cDNA subtraction method, we recently identified in irradiated cultured human thyroid cells a gene belonging to the PLKs family, the human homologue of mouse serum-inducible kinase (hSNK). Study of the gene structure revealed the presence of 14 exons spanning over 6 kb of genomic DNA, that encoded a 2.9 kb mRNA product ubiquitously expressed to a various extent in different human tissues. The 5'-flanking region of hSNK was examined to study tile basic transcriptional activity of the gene. The core promoter with activation elements including the TATA-like motif and GC box resided within the first 120 nucleotides, upstream of an analogous transcription start site. Functional mapping of the regulatory region demonstrated the presence of both enhancer and repressor fragments. Analysis of 0.7 kb of the 5'-upstream region of the gene revealed a number of motifs comprising of putative binding sites for several transcription factors and, notably, the p53 binding homology sequence. In conclusion, the hSNK may be a unique target molecule to influence cell fate following irradiation. (C) 2002 Elsevier Science B.V. All rights reserved.