Format

Send to

Choose Destination
Cell. 2005 Aug 12;122(3):393-405.

Regulation of nuclear proteasome by Rhp6/Ubc2 through ubiquitination and destruction of the sensor and anchor Cut8.

Author information

1
Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

Abstract

While proteasome is central to the degradation of cellular ubiquitinated proteins, the control of its nuclear function is barely understood. Here we show that the fission yeast ubiquitin-conjugating Rhp6/Ubc2/Rad6 and ligating enzymes Ubr1 are responsible for nuclear enrichment of proteasome through the function of Cut8, a nuclear envelope protein. Cut8 is an Rhp6 substrate that physically interacts with and tethers proteasome. Nonubiquitinatable K-all-R Cut8 weakly interacts with proteasome and fails to enrich nuclear proteasome. Consistently, the nuclear enrichment of proteasome also fails in rhp6 and ubr1 null mutants. Further, cut8 null and cut8 K-all-R mutants are hypersensitive to DNA damage, probably due to the paucity of nuclear proteasome. Thus, Rhp6 enhances the retention of nuclear proteasome through regulating Cut8. The short-lived nature of Cut8 is crucial for feedback enrichment of the proteasome within the nucleus. This is likely to be a conserved mechanism as we describe a Cut8 homolog in flies.

PMID:
16096059
DOI:
10.1016/j.cell.2005.05.023
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center