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Molecular and Cellular Biology
Article . 2005 . Peer-reviewed
License: ASM Journals Non-Commercial TDM
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Filamin A-Bound PEBP2β/CBFβ Is Retained in the Cytoplasm and Prevented from Functioning as a Partner of the Runx1 Transcription Factor

Authors: Megumi Nakazato; Kenji Tanabe; Masanobu Satake; Takehiro Ogata; Kazuyoshi Kohu; Toshio Watanabe; Naomi Yoshida; +4 Authors

Filamin A-Bound PEBP2β/CBFβ Is Retained in the Cytoplasm and Prevented from Functioning as a Partner of the Runx1 Transcription Factor

Abstract

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.

Keywords

Cell Nucleus, Cytoplasm, Filamins, Microfilament Proteins, Protein Structure, Tertiary, DNA-Binding Proteins, Mice, Contractile Proteins, Transcription Factor AP-2, Proto-Oncogene Proteins, Two-Hybrid System Techniques, Core Binding Factor Alpha 2 Subunit, Animals, Humans, RNA, Small Interfering, HeLa Cells, Protein Binding, Transcription Factors

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    45
    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
45
Top 10%
Top 10%
Top 10%
bronze