Filamin A-bound PEBP2beta/CBFbeta is retained in the cytoplasm and prevented from functioning as a partner of the Runx1 transcription factor.
The heterodimeric transcription factor PEBP2/CBF is composed of a DNA-binding subunit, called Runx1, and a non-DNA-binding subunit, called PEBP2beta/CBFbeta. The Runx1 protein is detected exclusively in the nuclei of most cells and tissues, whereas PEBP2beta is located in the cytoplasm. We addressed the mechanism by which PEBP2beta localizes to the cytoplasm and found that it is associated with filamin A, an actin-binding protein. Filamin A retains PEBP2beta in the cytoplasm, thereby hindering its engagement as a Runx1 partner. The interaction with filamin A is mediated by a region within PEBP2beta that includes amino acid residues 68 to 93. The deletion of this region or the repression of filamin A enables PEBP2beta to translocate to the nucleus. Based on these observations, we propose that PEBP2beta has two distinct domains, a newly defined regulatory domain that interacts with filamin A and the previously identified Runx1-binding domain.
Yoshida
Naomi
N
Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
Ogata
Takehiro
T
Tanabe
Kenji
K
Li
Songhua
S
Nakazato
Megumi
M
Kohu
Kazuyoshi
K
Takafuta
Toshiro
T
Shapiro
Sandor
S
Ohta
Yasutaka
Y
Satake
Masanobu
M
Watanabe
Toshio
T
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D064448:Filamins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D003285:Contractile Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D064448:Filamins; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors