Cyclin K as a direct transcriptional target of the p53 tumor suppressor.
Cyclin K, a newly recognized member of the "transcription" cyclin family, may play a dual role by regulating CDK and transcription. Using cDNA microarray technology, we found that cyclin K mRNA was dramatically increased in U373MG, a glioblastoma cell line deficient in wild-type p53, in the presence of exogenous p53. An electrophoretic mobility-shift assay showed that a potential p53-binding site (p53BS) in intron 1 of the cyclin K gene could indeed bind to p53 protein. Moreover, a heterologous reporter assay revealed that the p53BS possessed p53-dependent transcriptional activity. Colony-formation assays indicated that overexpression of cyclin K suppressed growth of T98G, U373MG and SW480 cells. The results suggested that cyclin K may play a role in regulating the cell cycle or apoptosis after being targeted for transcription by p53.
Mori
Toshiki
T
Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Anazawa
Yoshio
Y
Matsui
Kuniko
K
Fukuda
Seisuke
S
Nakamura
Yusuke
Y
Arakawa
Hirofumi
H
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D016213:Cyclins / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D005720:Gamma Rays; D015723:Gene Library; D016158:Genes, p53 / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011485:Protein Binding; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
C113028:CCNK protein, human; D016213:Cyclins; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin