Gris1, a new common integration site in Graffi murine leukemia virus-induced leukemias: overexpression of a truncated cyclin D2 due to alternative splicing.
The Graffi murine leukemia virus is a nondefective ecotropic retrovirus that was originally reported to induce myeloid leukemia in some strains of mice (A. Graffi, Ann. N.Y. Acad. Sci. 68:540-558, 1957). Using provirus-flanking sequences as DNA probes, we identified a new common retroviral integration site called Gris1 (for Graffi integration site 1). Viral integrations in Gris1 were detected in 13% of the tumors analyzed. The Gris1 locus was mapped to the distal region of mouse chromosome 6, 85 kb upstream of the cyclin D2 gene. Such viral integration in Gris1 causes overexpression of the normal 6.5-kb major transcript of cyclin D2 but also induces the expression of a new, alternatively spliced 1.1-kb transcript from the cyclin D2 gene that encodes a truncated cyclin D2 of 17 kDa. The expression of this 1.1-kb transcript is specific to tumors in which Gris1 is rearranged but is also detected at low levels in normal tissue.
Denicourt
Catherine
C
Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, Canada.
Kozak
Christine A
CA
Rassart
Eric
E
D016475:3T3 Cells; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D056742:Cyclin D2; D016213:Cyclins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007942:Leukemia, Experimental / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012192:Retroviridae Infections / Q000235:genetics*; D014412:Tumor Virus Infections / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics*; D014981:Xenopus
C080336:CCND2 protein, human; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins