Multifunctional Protein Contributes to Blood Cell Development

Source: Salk Institute

Summary: Researchers in a new finding has uncovered a previously unknown job for a protein called nucleoporin-Nup98 in mouse cells.

Nucleoporins are a family of around 30 proteins and are the main components of the nuclear pore complex (NPC). The NPC extends across the nuclear envelope and forms a gateway that regulates the transport of macromolecules between the cell nucleus and the cytoplasm. Recent studies have shown that a subset of nucleoporins can detach from the NPC and move into the nuclear interior to regulate transcription. One such nucleoporin is Nup98.

In a new finding, a team of researchers from the Salk Institute has uncovered a previously unknown job for the nucleoporin-Nup98 in mouse cells. In addition to helping control the movement of molecules in and out of the nucleus of the cell, they found that it also helps direct the blood cells development, enabling immature blood stem cells to differentiate into many specialized mature cell types. Further, they discovered the mechanism by which—when this differentiation process is disturbed can contribute to the formation of certain types of leukemia. The study findings were published in the journal Genes & Development.

Proteins of Nuclear Pore Complex

The localization of nup98 (green) in the nuclei (blue) of cancer cells. Credit: Salk Institute

Until now it was not known how nup98 regulates transcription mechanism. The researchers found that it acts through a link with a protein complex called Wdr82-Set1/COMPASS, which is part of the cell’s epigenetic machinery. The research findings establish a function of Nup98 in hematopoietic gene activation and provide mechanistic insight into which Nup98 leukemic fusion proteins promote acute myeloid leukemia (AML).

Senior author, Martin Hetzer said, “This is the first mechanistic insight of how one of these nup proteins works in mammals”, “We have only touched the surface here in uncovering how this evolutionarily conserved mechanism works in mammalian cells.”

More Information: Tobias M. Franks et al, “Nup98 recruits the Wdr82–Set1A/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells”, Genes & Development (2017).DOI:10.1101/gad.306753.117

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