Conserved regulation of the Jak/STAT pathway by the endosomal protein asrij maintains stem cell potency.
Asrij/OCIAD1 is an endosomal protein expressed in stem cells and cardiovascular lineages and aberrantly expressed in several cancers. We show that dose-dependent modulation of cytokine-dependent JAK/STAT signaling by Asrij regulates mouse embryonic stem cell pluripotency as well as Drosophila hematopoietic stem cell maintenance. Furthermore, mouse asrij can substitute for Drosophila ... asrij, indicating that they are true homologs. We identify a conserved region of Asrij that is necessary and sufficient for vesicular localization and function. We also show that Asrij and STAT3 colocalize in endosomes and interact biochemically. We propose that Asrij provides an endosomal scaffold for STAT3 interaction and activation, and may similarly control other circuits that maintain stemness. Thus, Asrij provides a key point of control for spatial and kinetic regulation of stem cell signals.
Mesh Terms:
Animals, Cell Differentiation, Cell Proliferation, Conserved Sequence, Drosophila, Drosophila Proteins, Endosomes, F-Box Proteins, HEK293 Cells, Hematopoietic Stem Cells, Humans, Janus Kinases, Membrane Proteins, Mice, Pluripotent Stem Cells, Protein Binding, Protein Transport, STAT3 Transcription Factor, Signal Transduction
Animals, Cell Differentiation, Cell Proliferation, Conserved Sequence, Drosophila, Drosophila Proteins, Endosomes, F-Box Proteins, HEK293 Cells, Hematopoietic Stem Cells, Humans, Janus Kinases, Membrane Proteins, Mice, Pluripotent Stem Cells, Protein Binding, Protein Transport, STAT3 Transcription Factor, Signal Transduction
Cell Rep
Date: Aug. 29, 2013
PubMed ID: 23972987
View in: Pubmed Google Scholar
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