The UBA2 domain functions as an intrinsic stabilization signal that protects Rad23 from proteasomal degradation.

The proteasome-interacting protein Rad23 is a long-lived protein. Interaction between Rad23 and the proteasome is required for Rad23's functions in nucleotide excision repair and ubiquitin-dependent degradation. Here, we show that the ubiquitin-associated (UBA)-2 domain of yeast Rad23 is a cis-acting, transferable stabilization signal that protects Rad23 from proteasomal degradation. Disruption ...
of the UBA2 domain converts Rad23 into a short-lived protein that is targeted for degradation through its N-terminal ubiquitin-like domain. UBA2-dependent stabilization is required for Rad23 function because a yeast strain expressing a mutant Rad23 that lacks a functional UBA2 domain shows increased sensitivity to UV light and, in the absence of Rpn10, severe growth defects. The C-terminal UBA domains of Dsk2, Ddi1, Ede1, and the human Rad23 homolog hHR23A have similar protective activities. Thus, the UBA2 domain of Rad23 is an evolutionarily conserved stabilization signal that allows Rad23 to interact with the proteasome without facing destruction.
Mesh Terms:
Blotting, Western, Cell Cycle Proteins, Cell Survival, DNA Repair, DNA Repair Enzymes, DNA-Binding Proteins, Flow Cytometry, Fungal Proteins, Hela Cells, Humans, Precipitin Tests, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin, Ultraviolet Rays
Mol. Cell
Date: Apr. 15, 2005
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