Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress.
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DNA damage triggers polyubiquitylation and degradation of the largest subunit of RNA polymerase II (RNAPII), a “mechanism of last resort” employed during transcription stress. In yeast, this process is dependent on Def1 through a previously unresolved mechanism. Here, we report that Def1 becomes activated through ubiquitylation- and proteasome-dependent processing. Def1 processing results in the removal of a domain promoting cytoplasmic localization, resulting in nuclear accumulation of the clipped protein. Nuclear Def1 then binds RNAPII, utilizing a ubiquitin-binding domain to recruit the Elongin-Cullin E3 ligase complex via a ubiquitin-homology domain in the Ela1 protein. This facilitates polyubiquitylation of Rpb1, triggering its proteasome-mediated degradation. Together, these results outline the multistep mechanism of Rpb1 polyubiquitylation triggered by transcription stress and uncover the key role played by Def1 as a facilitator of Elongin-Cullin ubiquitin ligase function.
Originalsprog | Engelsk |
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Tidsskrift | Cell |
Vol/bind | 154 |
Udgave nummer | 5 |
Sider (fra-til) | 983-995 |
ISSN | 0092-8674 |
DOI | |
Status | Udgivet - 2013 |
Eksternt udgivet | Ja |
ID: 331083929