Proviral integration of an Abelson-murine leukemia virus deregulates BKLF-expression in the hypermutating pre-B cell line 18-81.
The transcription factor BKLF (basic Krüppel-like factor, KLF3) is a member of the Krüppel-like factors (KLF) family. KLF members harbor a characteristic C-terminal zinc-finger DNA-binding domain and bind preferentially to CACCC-motifs. BKLF is highly expressed in haematopoietic and erythoid cells and works either as repressor or activator of transcription in various genes. BKLF-deficient mice display myeloproliferative disorders and abnormalities in haematopoiesis. Other members of the KLF-family such as GKLF and BCL11A have been implicated in tumorigenesis, however, for BKLF such association has not yet been demonstrated. We report here that a single Abelson-murine leukemia virus (A-MuLV) provirus is present in the genome of the hypermutating murine pre-B cell line 18-81. The provirus has integrated into the locus of the transcription factor BKLF. In contrast to other A-MuLV transformed pre-B cell lines, BKLF is highly transcribed in cell line 18-81. BKLF transcripts originate from the retroviral long terminal repeats (LTRs) and BKLF protein can be detected by gel shift retardation assay. We hypothesize on a potential role of BKLF deregulation in tumorigenesis and/or in the induction of somatic hypermutation in cell line 18-81.
Kirberg
Jörg
J
Max Planck Institute of Immunbiology, Stübeweg 51, D-79108 Freiburg, Germany.
Gschwendner
Claudia
C
Dangy
Jean-Pierre
JP
Rückerl
Florian
F
Frommer
Friederike
F
Bachl
Jürgen
J
D000011:Abelson murine leukemia virus / Q000235:genetics*; D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D017578:Immunoglobulin Class Switching; D000090062:Kruppel-Like Factor 4; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011533:Proviruses / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin; D020079:Terminal Repeat Sequences; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D012097:Repressor Proteins; D014157:Transcription Factors