InterPro domain: IPR038422

This entry includes fission yeast tethering factor for nuclear proteasome Cut8 protein and its homologue, Sts1.

In Schizosaccharomyces pombe, Cut8 is a nuclear envelope protein that physically interacts with and tethers 26S proteasome in the nucleus resulting in the nuclear accumulation of proteasome [ 1 ]. Cut8 comprises three functional domains. An N-terminal lysine-rich segment which binds to the proteasome when ubiquitinated, a central dimerisation domain and a C-terminal nine-helix, 3Q5W , bundle which shows structural similarity to 14-3-3 phosphoprotein-binding domains. The helical bundle is necessary for liposome and cholesterol binding [ 2 ]. Cut8 is a proteasome substrate and the N-terminal segment is polyubiquitinated and functions as a degron tag. Ubiquitination of the amino N-terminal segment is essential for the function of Cut8 [ 3 ]. Lysine residues in the N-terminal segment of Cut8 are required for physical interaction with proteasome [ 3 ]. In fission yeast the function of Cut8 has been demonstrated to be regulated by ubiquitin-conjugating Rhp6/Ubc2/Rad6 and ligating enzymes Ubr1 [ 3 ]. Cut8 homologues have been identified in Drosophila melanogaster, Anopheles gambiae and Dictyostelium discoideum [ 3 ].

1. Regulation of nuclear proteasome by Rhp6/Ubc2 through ubiquitination and destruction of the sensor and anchor Cut8. Cell 122, 393-405
2. Implications for proteasome nuclear localization revealed by the structure of the nuclear proteasome tether protein Cut8. Proc. Natl. Acad. Sci. U.S.A. 108, 16950-5