Radiation-inducible hSNK gene is transcriptionally regulated by p53 binding homology element in human thyroid cells.
We identified a species relevant to polo-like kinase family, a human homologue of mouse serum-inducible kinase, hSNK gene, whose mRNA expression was rapidly increased in cultured human thyroid cells after X-ray irradiation. The cDNA cloning and genomic analysis of the hSNK gene showed the presence of 14 exons spanning over 6 kb of genomic DNA that encodes a 2.9-kb mRNA product. Promoter analysis demonstrated possible existence of a radiation-responsive element in the p53 binding homology element (p53RE) localized to near upstream of basal promoter of the hSNK gene. Nuclear protein extracts from HeLa and various human thyroid carcinoma cell lines bound selectively to p53RE. Anti-p53 or anti-p73 antibodies, however, failed to recognize the p53RE-protein complex formed in the presence of such nuclear extracts. These results suggest that radiation-responsive transcription factor(s) directly participates in the regulation of hSNK gene expression via the binding to p53RE in promoter region.
Shimizu-Yoshida
Y
Y
Department of Nature Medicine, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Sugiyama
K
K
Rogounovitch
T
T
Ohtsuru
A
A
Namba
H
H
Saenko
V
V
Yamashita
S
S
D001483:Base Sequence; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005091:Exons; D017353:Gene Deletion; D015723:Gene Library; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011494:Protein Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D012313:RNA / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013961:Thyroid Gland / Q000378:metabolism* / Q000528:radiation effects*; D013964:Thyroid Neoplasms / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D012313:RNA; D004247:DNA; D008156:Luciferases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase