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<blockquote type=cite class=cite cite=""><br><br>
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SEMINARIO CONJUNTO QUÍMICA BIOLÓGICA / IFIBYNE<br><br>
VIERNES de octubre a las 15:30 h, Aula Cardini del Departamento de
Química<br>
Biológica, 4to piso.<br>
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<br>
Expositor: Anton Khmelinskii<br>
Center for Molecular Biology of the University of Heidelberg (ZMBH),<br>
DKFZ-ZMBH Alliance, Heidelberg, Germany.<br><br>
"Functional profiling of the ubiquitin-proteasome system of
protein<br>
degradation".<br><br>
Selective protein degradation contributes to cellular homeostasis
through<br>
removal of unnecessary or damaged proteins. The ubiquitin-proteasome<br>
system (UPS) plays a key role in selective protein degradation, whereby
a<br>
cascade of E1 ubiquitin-activating, E2 ubiquitin-conjugating and E3<br>
ubiquitin-protein ligase enzymes marks proteins with polyubiquitin
chains<br>
for degradation by the proteasome. Deubiquitinating enzymes (DUBs),
which<br>
remove ubiquitin marks from target proteins and replenish the pool of
free<br>
ubiquitin, are involved at various stages of the targeting and
degradation<br>
processes. Despite the central role of the UPS in protein
degradation,<br>
many UPS components are poorly characterized, various E3 ligases have
no<br>
known substrates and the functions of DUBs are not well understood.
To<br>
help bridge these gaps, we generated a genome-wide library tailored for
in<br>
vivo analysis of proteome dynamics in the budding yeast
Saccharomyces<br>
cerevisiae. This library consists of ~ 4000 strains each expressing
a<br>
different protein endogenously tagged with a tandem fluorescent
protein<br>
timer (tFT). The tFT is composed of two fluorescent proteins with
distinct<br>
kinetics of fluorophore maturation and reports on the abundance and<br>
degradation kinetics of the tagged proteins.<br>
We applied this resource to systematically analyze the role of
different<br>
UPS components in proteome turnover. Using synthetic genetic array<br>
technology followed by high-throughput whole colony fluorescence
imaging,<br>
the abundance and stability of each fusion in the tFT library were<br>
measured in strains carrying mutations in key UPS components. Our<br>
experiments provide evidence for the existence of a novel protein
quality<br>
control pathway at the inner nuclear membrane and it's interplay
with<br>
endoplasmic reticulum-associated protein degradation.<br>
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Los esperamos!<br>
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<br><br>
-- <br>
Alejandro Colman-Lerner </blockquote></body>
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