Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress.
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Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress. / Wilson, MD; Harreman, M; Taschner, M; Reid, J; Walker, J; Erdjument-Bromage, H; Tempst, P; Svejstrup, JQ.
I: Cell, Bind 154, Nr. 5, 2013, s. 983-995.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress.
AU - Wilson, MD
AU - Harreman, M
AU - Taschner, M
AU - Reid, J
AU - Walker, J
AU - Erdjument-Bromage, H
AU - Tempst, P
AU - Svejstrup, JQ
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2013.07.028
DO - 10.1016/j.cell.2013.07.028
M3 - Journal article
C2 - 23993092
VL - 154
SP - 983
EP - 995
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -
ID: 331083929