[Todos] SEMINARIO CONJUNTO QB/IFIBYNE - Viernes 24 de octubre 15:30 h - Anton Khmelinskii

[Claudia Sepúlveda]

RECORDATORIO

SEMINARIO CONJUNTO QUÍMICA BIOLÓGICA / IFIBYNE

VIERNES 24 de octubre a las 15:30 h, Aula Cardini del Departamento de
Química Biológica, 4to piso.
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Expositor: Anton Khmelinskii
Center for Molecular Biology of the University of Heidelberg (ZMBH),
DKFZ-ZMBH Alliance, Heidelberg, Germany.

"Functional profiling of the ubiquitin-proteasome system of protein
degradation".

Selective protein degradation contributes to cellular homeostasis through
removal of unnecessary or damaged proteins. The ubiquitin-proteasome
system (UPS) plays a key role in selective protein degradation, whereby a
cascade of E1 ubiquitin-activating, E2 ubiquitin-conjugating and E3
ubiquitin-protein ligase enzymes marks proteins with polyubiquitin chains
for degradation by the proteasome. Deubiquitinating enzymes (DUBs), which
remove ubiquitin marks from target proteins and replenish the pool of free
ubiquitin, are involved at various stages of the targeting and degradation
processes. Despite the central role of the UPS in protein degradation,
many UPS components are poorly characterized, various E3 ligases have no
known substrates and the functions of DUBs are not well understood. To
help bridge these gaps, we generated a genome-wide library tailored for in
vivo analysis of proteome dynamics in the budding yeast Saccharomyces
cerevisiae. This library consists of ~ 4000 strains each expressing a
different protein endogenously tagged with a tandem fluorescent protein
timer (tFT). The tFT is composed of two fluorescent proteins with distinct
kinetics of fluorophore maturation and reports on the abundance and
degradation kinetics of the tagged proteins.
We applied this resource to systematically analyze the role of different
UPS components in proteome turnover. Using synthetic genetic array
technology followed by high-throughput whole colony fluorescence imaging,
the abundance and stability of each fusion in the tFT library were
measured in strains carrying mutations in key UPS components. Our
experiments provide evidence for the existence of a novel protein quality
control pathway at the inner nuclear membrane and it's interplay with
endoplasmic reticulum-associated protein degradation.
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Los esperamos!