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.
Knauer
Shirley K
SK
Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Str. 42-44, D-60596 Frankfurt, Germany.
Carra
Gert
G
Stauber
Roland H
RH
D021581:Active Transport, Cell Nucleus; D000818:Animals; D005075:Biological Evolution; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019913:Nuclear Localization Signals; D010740:Phospholipases / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein
D005136:Eye Proteins; D018398:Homeodomain Proteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D010740:Phospholipases; D018160:Receptors, Cytoplasmic and Nuclear; D029961:Zebrafish Proteins; D000097606:Exportin 1 Protein; C108838:vsx1 protein, zebrafish