Oncogenic potential of the DNA replication licensing protein CDT1.
The expression of a gene, designated as Retroviral insertion site (Ris)2, was activated by retroviral DNA integration in an immortalized primitive erythroid cell line, EB-PE. Ris2 was also expressed at high levels in all human tumor cell lines analysed. Consistently, NIH3T3 fibroblasts overexpressing Ris2 formed tumors in Rag2 -/- mice when injected subcutaneously. The putative RIS2 protein shows a high sequence similarity to Xenopus CDT1, Drosophila DUP, and human CDT1, a newly identified DNA replication licensing protein, suggesting that Ris2 is a mouse homologue of CDT1. Cells overexpressing Ris2/Cdt1 exhibited a quicker entry into S phase when released from serum starvation compared to controls. Our results suggest that CDT1, an essential licensing protein for DNA replication, can function as an oncogene in mammals.
Arentson
Elizabeth
E
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA.
Faloon
Patrick
P
Seo
Junghee
J
Moon
Eunpyo
E
Studts
Joey M
JM
Fremont
Daved H
DH
Choi
Kyunghee
K
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014981:Xenopus / Q000235:genetics; D029867:Xenopus Proteins
C406819:Cdt1 protein, Xenopus; D018797:Cell Cycle Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C498645:Ris2 protein, mouse; D029867:Xenopus Proteins