Open AccessThe Sts1 nuclear import adaptor uses a noncanonical bipartite NLS and is directly degraded by the proteasome
Author(s) -
Lauren Budenholzer,
Carolyn Breckel,
Christopher M. Hickey,
Mark Hochstrasser
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.236158
Subject(s) - karyopherin , proteasome , nls , nuclear localization sequence , biology , nuclear transport , microbiology and biotechnology , ubiquitin , importin , nucleus , nuclear protein , biochemistry , cell nucleus , transcription factor , gene
The proteasome is an essential regulator of protein homeostasis. In yeast and many mammalian cells, proteasomes strongly concentrate in the nucleus. Yeast Sts1 is an essential protein linked to proteasome nuclear localization. Here we show that Sts1 contains a noncanonical bipartite nuclear localization signal (NLS) important for both nuclear localization of Sts1 itself and the proteasome. Sts1 binds the karyopherin-α import receptor (Srp1) stoichiometrically, and this requires the NLS. The NLS is essential for viability, and overexpressed Sts1 with an inactive NLS interferes with 26S proteasome import. The Sts1-Srp1 complex binds preferentially to fully assembled 26S proteasomes in vitro. Sts1 is itself a rapidly degraded 26S proteasome substrate; notably, this degradation is ubiquitin-independent in cells and in vitro and is inhibited by Srp1 binding. Mutants of Sts1 are stabilized, suggesting its degradation is tightly linked to its role in localizing proteasomes to the nucleus. We propose that Sts1 normally promotes nuclear import of fully assembled proteasomes and is directly degraded by proteasomes without prior ubiquitylation following karyopherin-α release in the nucleus.