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Molecular and Cellular Biology, December 2000, p. 9281-9293, Vol. 20, No. 24
Department of Genetics1 and
Department of Tumor Cell Biology,3 St.
Jude Children's Research Hospital, Memphis, Tennessee 38105, and
Department of Pathology, Erasmus University, 3000 DR Rotterdam,
The Netherlands2
Received 1 September 2000/Accepted 20 September 2000
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
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The MN1-TEL Fusion Protein, Encoded by the Translocation
(12;22)(p13;q11) in Myeloid Leukemia, Is a Transcription Factor
with Transforming Activity
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.
*
Corresponding author. Present address for Arjan Buijs:
Department of Hematology, University Medical Center Utrecht,
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Phone:
31-30-2507769. Fax: 31-30-2511893. E-mail:
a.buijs{at}lab.azu.nl. Mailing address for Gerard C. Grosveld: Department of Genetics, St. Jude Children's Research
Hospital, Memphis, TN 38105. Phone: (901) 495-2692. Fax: (901)
526-2907. E-mail: gerard.grosveld{at}stjude.org.
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