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PMID: 15767664 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nuclear export is evolutionarily conserved in CVC paired-like homeobox proteins and influences protein stability, transcriptional activation, and extracellular secretion.

Molecular and cellular biology ·Vol. 25 ·No. 7 ·2005-04-00 ·Pages 2573-82

Knauer SK, Carra G, Stauber RH

Abstract

Homeodomain transcription factors control a variety of essential cell fate decisions during development. To understand the developmental regulation by these transcription factors, we describe here the molecular analysis of paired-like CVC homeodomain protein (PLC-HDP) trafficking. Complementary experimental approaches demonstrated that PLC-HDP family members are exported by the Crm1 pathway and contain an evolutionary conserved leucine-rich nuclear export signal. Importantly, inactivation of the nuclear export signal enhanced protein stability, resulting in increased transactivation of transfected reporters and decreased extracellular secretion. In addition, PLC-HDPs harbor a conserved active nuclear import signal that could also function as a protein transduction domain. In our study, we characterized PLC-HDPs as mobile nucleocytoplasmic shuttle proteins with the potential for unconventional secretion and intercellular transfer. Nucleocytoplasmic transport may thus represent a conserved control mechanism to fine-tune the transcriptional activity of PLC-HDPs prerequisite for regulating and maintaining the complex expression pattern during development.

MeSH Terms
Active Transport, Cell Nucleus Animals Biological Evolution Cell Line Cell Nucleus/metabolism Eye Proteins/genetics,metabolism Homeodomain Proteins/chemistry,genetics,metabolism Humans Karyopherins/genetics,metabolism Mice Nuclear Localization Signals Phospholipases/chemistry,metabolism Protein Binding Receptors, Cytoplasmic and Nuclear/genetics,metabolism Signal Transduction Transcriptional Activation Zebrafish Zebrafish Proteins/genetics,metabolism
Chemicals
Eye Proteins Homeodomain Proteins Karyopherins Nuclear Localization Signals Receptors, Cytoplasmic and Nuclear Zebrafish Proteins exportin 1 protein vsx1 protein, zebrafish Phospholipases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Knauer Shirley K
Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Str. 42-44, D-60596 Frankfurt, Germany.
Carra Gert
Stauber Roland H
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.7.2573-2582.2005
Published
2005-04-00
Pages
2573-82
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1061648
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.25.7.2573-2582.2005 PMC Full Text View journal details
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