Protein biogenesis and quality control

in the secretory pathway

The Kopito laboratory seeks a molecular understanding of how cells maintain the fidelity of their proteomes. Unlike DNA, which can be repaired if damaged or incorrectly made, proteins cannot be mended. Instead, damaged or incorrectly synthesized proteins must be rapidly and efficiently destroyed lest they form toxic aggregates. Our laboratory use state-of-the-art cell biological, genetic and systems-level approaches to understand how proteins are correctly synthesized, folded and assembled in the mammalian secretory pathway, how errors in this process are detected and how abnormal proteins are destroyed by the ubiquitin-proteasome system. 



Pataki et al, PNAS 2018

"Proteomic analysis of monolayer-integrated proteins on lipid droplets identifies amphipathic interfacial α-helical membrane anchors"

CRISPR G-abstract.jpg

Leto et al,  Mol Cell 2019

"Genome-wide CRISPR Analysis Identifies Substrate-Specific Conjugation Modules in ER-Associated Degradation"

UFM1 Graphical AbstractV3.png

Walczak et al, PNAS 2019

"Ribosomal protein RPL26 is the principal target of UFMylation"

How do proteins integrate into only a single leaflet of a lipid bilayer? Cool application of multiplex isobaric tags to identify the MIP-ome (the monolayer-integrated proteome) 

Parallel genome-wide CRISPR screens map substrate selectivity and identify a role for unconventional ubiquitin linkages in ERAD

UFMylation pathway identified in genetic screen for ERAD; RPL26 is major target for UFM1 conjugation pathway at the ER membrane