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An actin-regulated importin α/β-dependent extended bipartite NLS directs nuclear import of MRTF-A
- Source :
- The EMBO Journal
- Publication Year :
- 2010
-
Abstract
- An actin-regulated importin α/β-dependent extended bipartite NLS directs nuclear import of MRTF-A The transcriptional coactivator MRTF-A/Mal binds G-actin, which sequesters it in the cytoplasm. In this study, Treisman and colleagues identify an unusual bipartite nuclear localisation signal in MRTF-A, and show that importin α/β-mediated import through this NLS is directly inhibited by G-actin binding.<br />Myocardin-related transcription factors (MRTFs) are actin-regulated transcriptional coactivators, which bind G-actin through their N-terminal RPEL domains. In response to signal-induced actin polymerisation and concomitant G-actin depletion, MRTFs accumulate in the nucleus and activate target gene transcription through their partner protein SRF. Nuclear accumulation of MRTFs in response to signal is inhibited by increased G-actin level. Here, we study the mechanism by which MRTF-A enters the nucleus. We show that MRTF-A contains an unusually long bipartite nuclear localisation signal (NLS), comprising two basic elements separated by 30 residues, embedded within the RPEL domain. Using siRNA-mediated protein depletion in vivo, and nuclear import assays in vitro, we show that the MRTF-A extended bipartite NLS uses the importin (Imp)α/β-dependent import pathway, and that import is inhibited by G-actin. Interaction of the NLS with the Impα–Impβ heterodimer requires both NLS basic elements, and is dependent on the Impα major and minor binding pockets. Binding of the Impα–Impβ heterodimer to the intact MRTF-A RPEL domain occurs competitively with G-actin. Thus, MRTF-A contains an actin-sensitive nuclear import signal.
- Subjects :
- CELLULAR PROLIFERATION
NF-KAPPA-B
Nuclear Localization Signals
environment and public health
Mice
PROTEIN IMPORT
SERUM RESPONSE FACTOR
0303 health sciences
General Neuroscience
030302 biochemistry & molecular biology
beta Karyopherins
Cell biology
medicine.anatomical_structure
Biochemistry
RPEL MOTIFS
Beta Karyopherins
RNA Interference
SRF
actin
STRUCTURAL BASIS
alpha Karyopherins
CRYSTALLOGRAPHIC ANALYSIS
Recombinant Fusion Proteins
education
Molecular Sequence Data
Active Transport, Cell Nucleus
NLS
Importin
Biology
General Biochemistry, Genetics and Molecular Biology
Article
DIFFERENTIAL EXPRESSION
03 medical and health sciences
MRTF
medicine
importin
Animals
Amino Acid Sequence
KARYOPHERIN ALPHA
Molecular Biology
Transcription factor
030304 developmental biology
Cell Nucleus
General Immunology and Microbiology
Alpha Karyopherins
Actins
Cell nucleus
NIH 3T3 Cells
Trans-Activators
LOCALIZATION SIGNALS
Nuclear transport
118 Biological sciences
Nuclear localization sequence
Subjects
Details
- ISSN :
- 14602075
- Volume :
- 29
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- The EMBO journal
- Accession number :
- edsair.doi.dedup.....6083040fc7ce9fa624adf01a406b3cd9