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PMID: 15657428 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Filamin A-bound PEBP2beta/CBFbeta is retained in the cytoplasm and prevented from functioning as a partner of the Runx1 transcription factor.

Molecular and cellular biology ·Vol. 25 ·No. 3 ·2005-02-00 ·Pages 1003-12

Yoshida N, Ogata T, Tanabe K, Li S, Nakazato M, Kohu K, Takafuta T, Shapiro S, Ohta Y, Satake M, Watanabe T

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.

MeSH Terms
Animals Cell Nucleus/metabolism Contractile Proteins/metabolism Core Binding Factor Alpha 2 Subunit Cytoplasm/metabolism DNA-Binding Proteins/metabolism Filamins HeLa Cells Humans Mice Microfilament Proteins/metabolism Protein Binding Protein Structure, Tertiary Proto-Oncogene Proteins/metabolism RNA, Small Interfering/metabolism Transcription Factor AP-2 Transcription Factors/metabolism Two-Hybrid System Techniques
Chemicals
Contractile Proteins Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins Filamins Microfilament Proteins Proto-Oncogene Proteins RNA, Small Interfering RUNX1 protein, human Runx1 protein, mouse Transcription Factor AP-2 Transcription Factors
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Yoshida Naomi
Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
Ogata Takehiro
Tanabe Kenji
Li Songhua
Nakazato Megumi
Kohu Kazuyoshi
Takafuta Toshiro
Shapiro Sandor
Ohta Yasutaka
Satake Masanobu
Watanabe Toshio
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39 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.3.1003-1012.2005
Published
2005-02-00
Pages
1003-12
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC543995
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.25.3.1003-1012.2005 PMC Full Text View journal details
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