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

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, Eye Proteins, Homeodomain Proteins, Humans, Karyopherins, Mice, Nuclear Localization Signals, Phospholipases, Protein Binding, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Transcriptional Activation, Zebrafish, Zebrafish Proteins
Mol. Cell. Biol.
Date: Apr. 01, 2005
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