Effects of PU.1-induced mouse calcium-calmodulin-dependent kinase I-like kinase (CKLiK) on apoptosis of murine erythroleukemia cells.
PU.1, a hematopoietic cell-specific Ets family transcription factor, is involved in the generation of murine erythroleukemia (MEL). To identify the target gene(s) of PU.1 in MEL cells, we carried out differential display (DD) analysis and isolated a novel gene whose expression was up-regulated after overexpression of PU.1 in MEL cells. Because the gene exhibited about 90% homology with the human calcium-calmodulin-dependent kinase I-like kinase (CKLiK) gene, it was identified as a mouse homologue of human CKLiK. The mCKLiK gene was mapped to the mouse chromosome 2A1-A3 region and shown to be expressed predominantly in T cells lymphoma and embryonal carcinoma cell lines and primary thymus and brain. Two types of transcripts were present showing a difference in the 3' portion of the coding region and CREB-activating ability. Overexpression of each isoform of mCKLiK in MEL cells revealed that one of them induces, while the other inhibits apoptosis under low serum condition. Differentiation inhibition and lineage switch to myelomonocytes, which were previously observed in MEL cells overexpressing PU.1, were not provoked in the cells overexpressing mCKLiK. These results suggest that mCKLiK is up-regulated by PU.1 in MEL cells and involved in apoptosis of the cells.
Department of Cell Genetics, Sasaki Institute, Tokyo 101-0062, Japan. oikawa@sasaki.or.jp
Toshiyuki
T
Yamada
Mitsuhiro
M
Suzuki
Hitoshi
H
Satoh
Fumiko
F
Kihara-Negishi
Hiroyasu
H
Nakano
Tsuneyuki
T
Oikawa
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005622:Friend murine leukemia virus; D015870:Gene Expression; D005914:Globins / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005914:Globins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C517596:CAMK1 protein, human; C517601:CAMK1D protein, human; C517598:Camk1 protein, mouse; C517602:Camk1d protein, mouse; C517681:Pnck protein, mouse