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Molecular and Cellular Biology, February 2005, p. 1003-1012, Vol. 25, No. 3
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.3.1003-1012.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Filamin A-Bound PEBP2ß/CBFß Is Retained in the Cytoplasm and Prevented from Functioning as a Partner of the Runx1 Transcription Factor

Naomi Yoshida,1 Takehiro Ogata,1 Kenji Tanabe,1 Songhua Li,1 Megumi Nakazato,1 Kazuyoshi Kohu,1 Toshiro Takafuta,2 Sandor Shapiro,3 Yasutaka Ohta,4 Masanobu Satake,1 and Toshio Watanabe1*

Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai,1 Hematology and Clinical Immunology, Nishi-Kobe Medical Center, Kobe, Japan,2 Department of Physiology, Jefferson Medical College, Philadelphia, Pennsylvania,3 Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts4

Received 6 May 2004/ Returned for modification 2 July 2004/ Accepted 26 October 2004

The heterodimeric transcription factor PEBP2/CBF is composed of a DNA-binding subunit, called Runx1, and a non-DNA-binding subunit, called PEBP2ß/CBFß. The Runx1 protein is detected exclusively in the nuclei of most cells and tissues, whereas PEBP2ß is located in the cytoplasm. We addressed the mechanism by which PEBP2ß localizes to the cytoplasm and found that it is associated with filamin A, an actin-binding protein. Filamin A retains PEBP2ß in the cytoplasm, thereby hindering its engagement as a Runx1 partner. The interaction with filamin A is mediated by a region within PEBP2ß that includes amino acid residues 68 to 93. The deletion of this region or the repression of filamin A enables PEBP2ß to translocate to the nucleus. Based on these observations, we propose that PEBP2ß has two distinct domains, a newly defined regulatory domain that interacts with filamin A and the previously identified Runx1-binding domain.


* Corresponding author. Mailing address: Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan. Phone: 81(22) 717-8478. Fax: 81 (22) 717-8482. E-mail: watanabe{at}idac.tohoku.ac.jp.


Molecular and Cellular Biology, February 2005, p. 1003-1012, Vol. 25, No. 3
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.3.1003-1012.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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