Reactome | NEK6/NEK7 phosphorylates NUP98

NEK6/NEK7 phosphorylates NUP98

Stable Identifier

R-HSA-2990880

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nuclear envelope, cytosol, nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Cell Cycle, Mitotic (Homo sapiens)
  - M Phase (Homo sapiens)
    - Mitotic Prophase (Homo sapiens)
      - Nuclear Envelope Breakdown (Homo sapiens)
        
        Nuclear Pore Complex (NPC) Disassembly (Homo sapiens)
        
        NEK6/NEK7 phosphorylates NUP98 (Homo sapiens)

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Phosphorylation of NUP98 by NEK6 (and/or NEK7) promotes nuclear envelope permeabilization by initiating nuclear pore complex (NPC) disassembly. Two NUP98 serine residues, S591 and S822 (referring to NUP98 splice variant NUP98-4; these residues correspond to S608 and S839 of NUP98 splice variant NUP98-3), are phosphorylated on NUP98 isolated from mitotic HeLa cells (human cervical cancer cell line). These serine residues match the NEK6 target site consensus and are phosphorylated by NEK6 in vitro. Both sites can also be phosphorylated in vitro by NEK7 and weakly by NEK2. As NEK7 but not NEK2 was shown to be involved, with NEK6, in nuclear envelope permeabilization, NEK2 is not shown as the NUP98 kinase. Phosphorylated NUP98 dissociates from the NPC (Laurell et al. 2011). As NUP98 localizes to both sides of the NPC, cytosolic and nucleoplasmic (Griffis et al. 2003), the reaction shows a portion of NUP98 being released to the cytosol, and a portion of NUP98 dissociating into the nucleus, similar to what is observed by immunocytochemistry (Laurell et al. 2011).

Literature References

PubMed ID	Title	Journal	Year
21335236	Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry Aebersold, R, Beck, K, Antonin, W, Krupina, K, Horvath, P, Bodenmiller, B, Theerthagiri, G, Laurell, E, Kutay, U	Cell	2011
12589057	Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes Powers, MA, Xu, S, Griffis, ER	Mol. Biol. Cell	2003