Biological implications of filamin A-bound PEBP2β/CBFβ retention in the cytoplasm

Toshio Watanabe, Naomi Yoshida, Masanobu Satake

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Multiple mechanisms regulate dynamic cytoplasmic-to-nuclear transport of transcription factors. However, little is known about the involvement of cytoskeletal proteins in this process. The heterodimeric transcription factor PEBP2/CBF is composed of a DNA-binding subunit, Runx1, and a non-DNA-binding subunit, PEBP2β/CBFβ. The Runx1 protein possesses nuclear localization signals and is found exclusively in the nucleus, whereas PEBP2β is located in the cytoplasm in most cells and tissues examined thus far. We investigated the mechanism by which PEBP2β localizes to the cytoplasm and found that it associates with filamin A, an actin-binding cytoskeletal protein. Filamin A retains PEBP2β in the cytoplasm, thereby hindering its engagement as a Runx1 partner. When filamin A is absent, PEBP2β moves into the nucleus and enhances Runx1-dependent transcription. These observations highlight the significance of the subcellular localization of PEBP2β in regulating its activity as a component of the PEBP2/CBF transcription factor. In humans, PEBP2β is frequently targeted in the leukemia-associated chromosomal abnormality, inversion 16 (inv 16). Thus, identifying the factors that mediate the subcellular localization of the PEBP2β-derived chimeric transcription factor produced by inv 16 is an important issue that will need to be resolved in order to understand the mechanism(s) involved in inv 16-induced leukemogenesis.

Original languageEnglish
Pages (from-to)197-205
Number of pages9
JournalCritical Reviews in Eukaryotic Gene Expression
Volume15
Issue number3
Publication statusPublished - 2005 Dec 1

Keywords

  • Cytoskeleton
  • Human skeletal disorders
  • Inversion 16
  • Subcellular localization

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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