Crystal Structure of the Nuclear Matrix Targeting Signal of the Transcription Factor Acute Myelogenous Leukemia-1/Polyoma Enhancer-binding Protein 2αB/Core Binding Factor α2*
- Lei Tang‡,
- Bo Guo§,
- Amjad Javed§,
- Je-Yong Choi§,
- Scott Hiebert¶,
- Jane B. Lian§,
- André J. van Wijnen§,
- Janet L. Stein§,
- Gary S. Stein§ and
- G. Wayne Zhou‡‖
- From the ‡Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, the§Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, and the¶Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146
Abstract
Transcription factors of the acute myelogenous leukemia (AML)/polyoma enhancer-binding protein (PEBP2α)/core-binding factor α (CBFA) class are key transactivators of tissue-specific genes of the hematopoietic and bone lineages. AML-1/PEBP2αB/CBFA2 proteins participating in transcription are associated with the nuclear matrix. This association is solely dependent on a highly conserved C-terminal protein segment, designated the nuclear matrix targeting signal (NMTS). The NMTS of AML-1 is physically distinct from the nuclear localization signal, operates autonomously, and supports transactivation. Our data indicate that the related AML-3 and AML-2 proteins are also targeted to the nuclear matrix in situ by analogous C-terminal domains. Here we report the first crystal structure of an NMTS in an AML-1 segment fused to glutathione S-transferase. The model of the NMTS consists of two loops connected by a flexible U-shaped peptide chain.
Footnotes
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↵* This work was supported by a Career Development Award from the American Diabetes Association and National Institutes of Health Grant AR 45688.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‖ To whom correspondence should be addressed. Tel.: 508-856-6869; Fax: 508-856-1218; E-mail: g.zhou@ummed.edu.
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↵2 J.-Y. Choi, A. Javed, S. K. Zaidi, S. Hiebert, J. B. Lian, A. J. van Wijnen, J. L. Stein, and G. S. Stein, unpublished data.
- Abbreviations:
- AML
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acute myelogenous leukemia
- PEBP
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polyoma enhancer-binding protein
- CBF
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core binding factor α
- NMTS
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nuclear matrix targeting signal
- GST
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glutathione S-transferase
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- Received June 7, 1999.
- Revision received July 23, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
