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Molecular and Cellular Biology, December 2000, p. 9281-9293, Vol. 20, No. 24
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

Arjan Buijs,1,* Luc van Rompaey,1 Anco C. Molijn,2 J. Nathan Davis,3 Alfred C. O. Vertegaal,1 Mark D. Potter,1 Constantin Adams,1 Sjozèf van Baal,1 Ellen C. Zwarthoff,2 Martine F. Roussel,3 and Gerard C. Grosveld1,*

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 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.

* 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.

Molecular and Cellular Biology, December 2000, p. 9281-9293, Vol. 20, No. 24
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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