Identification of Notch1 as a frequent target for provirus insertional mutagenesis in T-cell lymphomas induced by leukemogenic mutants of mouse mammary tumor virus.
In contrast to wild-type mouse mammary tumor virus (MMTV), the MMTV mutants with specific deletions in the U3 region of their long terminal repeats cause T-cell lymphomas. In 30% of T-cell lymphomas arising in BALB/c mice infected with MLA-MMTV, a leukemogenic MMTV mutant, we have found that MMTV proviruses were integrated into a short region of the Notch1 genome, so that truncated Notch1 transcripts encoding the transmembrane and the cytoplasmic domains of Notch1 protein could be expressed. Thus, Notch1 is a major target of provirus insertional mutagenesis in these T-cell lymphomas.
Yanagawa
S
S
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. syanagaw@virus.kyoto-u.ac.jp
Lee
J S
JS
Kakimi
K
K
Matsuda
Y
Y
Honjo
T
T
Ishimoto
A
A
D000818:Animals; D001483:Base Sequence; D015321:Gene Rearrangement; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000821:virology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011533:Proviruses / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D020079:Terminal Repeat Sequences; D014157:Transcription Factors
D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors