Thyroglobulin interactome profiling defines altered proteostasis topology associated with thyroid dyshormonogenesis.

Molecular & Cellular Proteomics : MCP
Madison T WrightLars Plate

Abstract

Thyroglobulin (Tg) is a secreted iodoglycoprotein serving as the precursor for T3 and T4 hormones. Many characterized Tg gene mutations produce secretion-defective variants resulting in congenital hypothyroidism (CH). Tg processing and secretion is controlled by extensive interactions with chaperone, trafficking, and degradation factors comprising the secretory proteostasis network. While dependencies on individual proteostasis network components are known, the integration of proteostasis pathways mediating Tg protein quality control and the molecular basis of mutant Tg misprocessing remain poorly understood. We employ a multiplexed quantitative affinity purification-mass spectrometry approach to define the Tg proteostasis interactome and changes between WT and several CH-variants. Mutant Tg processing is associated with common imbalances in proteostasis engagement including increased chaperoning, oxidative folding, and engagement by targeting factors for ER-associated degradation (ERAD). Furthermore, we reveal mutation-specific changes in engagement with N-glycosylation components, suggesting distinct requirements for one Tg variant on dual engagement of both oligosaccharyltransferase complex isoforms for degradation. Modulati...Continue Reading

References

Sep 1, 1993·The American Journal of Physiology·P S KimP Arvan
Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·C HammondA Helenius
Mar 1, 2003·Science·Maurizio MolinariPaolo Paganetti
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Jan 25, 2006·The Journal of Biological Chemistry·Kazuyoshi HiraoNobuko Hosokawa
Jun 3, 2006·Pediatrics·Susan R RoseSurendra K Varma
Aug 15, 2006·Structure·Guennadi KozlovKalle Gehring
May 30, 2007·Clinical Endocrinology·Mariela CaputoHéctor M Targovnik
Jun 19, 2007·Best Practice & Research. Clinical Endocrinology & Metabolism·Alexis Oetting, Paul M Yen
Jan 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Walid AwadLinda M Hendershot
Jul 4, 2008·The Journal of Clinical Investigation·Jaemin LeePeter Arvan
Jul 18, 2008·Thyroid : Official Journal of the American Thyroid Association·Viviane PardoGeraldo Medeiros-Neto
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jan RiemerLars Ellgaard
Jul 22, 2011·Nature·F Ulrich HartlManajit Hayer-Hartl
Aug 6, 2011·The Journal of Biological Chemistry·Jaemin LeePeter Arvan
Aug 31, 2011·Methods in Molecular Biology·Mihaela E Sardiu, Michael P Washburn
Nov 29, 2011·Nature Cell Biology·John C ChristiansonRon R Kopito
Feb 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Benedict C S CrossHeather P Harding
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Jun 22, 2014·Advances in Experimental Medicine and Biology·Hanna G Budayeva, Ileana M Cristea

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Dec 11, 2020·Experimental Cell Research·Madison T Wright, Lars Plate

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