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Global Analysis of Intercellular Homeodomain Protein Transfer

Author:
Lee, Eun Jung  Kim, Namsuk  Park, Jun Woo  Kang, Kyung Hwa  Kim, Woo-il  Sim, Nam Suk  Jeong, Chan-Seok  Blackshaw, Seth  Vidal, Marc  Huh, Sung-Oh  Kim, Dongsup  Lee, Jeong Ho  Kim, Jin Woo  


Journal:
CELL REPORTS


Issue Date:
2019


Abstract(summary):

The homeodomain is found in hundreds of transcription factors that play roles in fate determination via cell-autonomous regulation of gene expression. However, some homeodomain-containing proteins (HPs) are thought to be secreted and penetrate neighboring cells to affect the recipient cell fate. To determine whether this is a general characteristic of HPs, we carried out a large-scale validation for intercellular transfer of HPs. Our screening reveals that intercellular transfer is a general feature of HPs, but it occurs in a cell-context-sensitive manner. We also found the secretion is not solely a function of the homeodomain, but it is supported by external motifs containing hydrophobic residues. Thus, mutations of hydrophobic residues of HPs abrogate secretion and consequently interfere with HP function in recipient cells. Collectively, our study proposes that HP transfer is an intercellular communication method that couples the functions of interacting cells.


Page:
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