The MN1-TEL fusion protein, encoded by the translocation (12;22)(p13;q11) in myeloid leukemia, is a transcription factor with transforming activity.
The Tel gene (or ETV6) is the target of the translocation (12;22)(p13;q11) in myeloid leukemia. TEL is a member of the ETS family of transcription factors and contains the pointed protein interaction (PNT) domain and an ETS DNA binding domain (DBD). By contrast to other chimeric proteins that contain TEL's PNT domain, such as TEL-platelet-derived growth factor beta receptor in t(5;12)(q33;p13), MN1-TEL contains the DBD of TEL. The N-terminal MN1 moiety is rich in proline residues and contains two polyglutamine stretches, suggesting that MN1-TEL may act as a deregulated transcription factor. We now show that MN1-TEL type I, unlike TEL and MN1, transforms NIH 3T3 cells. The transforming potential depends on both N-terminal MN1 sequences and a functional TEL DBD. Furthermore, we demonstrate that MN1 has transcription activity and that MN1-TEL acts as a chimeric transcription factor on the Moloney sarcoma virus long terminal repeat and a synthetic promoter containing TEL binding sites. The transactivating capacity of MN1-TEL depended on both the DBD of TEL and sequences in MN1. MN1-TEL contributes to leukemogenesis by a mechanism distinct from that of other chimeric proteins containing TEL.
Buijs
A
A
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. a.buijs@lab.azu.nl
van Rompaey
L
L
Molijn
A C
AC
Davis
J N
JN
Vertegaal
A C
AC
Potter
M D
MD
Adams
C
C
van Baal
S
S
Zwarthoff
E C
EC
Roussel
M F
MF
Grosveld
G C
GC
D000818:Animals; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005809:Genes, Regulator; D006801:Humans; D015151:Immunoblotting; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D018613:Microscopy, Confocal; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D004247:DNA; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C417770:MN1-TEL fusion protein, human