Cells rely on protein homeostasis to maintain proper biological functions. Dysregulation of protein homeostasis contributes to the pathogenesis of many neurodegenerative diseases and cancers. Ubiquilins (UBQLNs) are versatile proteins that engage with many components of protein quality control (PQC) machinery in cells. Disease-linked mutations of UBQLNs are most commonly associated with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative disorders. UBQLNs play well-established roles in PQC processes, including facilitating degradation of substrates through the ubiquitin–proteasome system (UPS), autophagy, and endoplasmic-reticulum-associated protein degradation (ERAD) pathways. In addition, UBQLNs engage with chaperones to sequester, degrade, or assist repair of misfolded client proteins. Furthermore, UBQLNs regulate DNA damage repair mechanisms, interact with RNA-binding proteins (RBPs), and engage with cytoskeletal elements to regulate cell differentiation and development. Important to the myriad functions of UBQLNs are its multidomain architecture and ability to self-associate. UBQLNs are linked to numerous types of cellular puncta, including stress-induced biomolecular condensates, autophagosomes, aggresomes, and aggregates. In this review, we focus on deciphering how UBQLNs function on a molecular level. We examine the properties of oligomerization-driven interactions among the structured and intrinsically disordered segments of UBQLNs. These interactions, together with the knowledge from studies of disease-linked mutations, provide significant insights to UBQLN structure, dynamics and function.
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September 2020
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Cover Image
Thermogenesis of Arum maculatum. The cover of this issue of the Biochemical Journal features an image from Ito et al., who report the temperature-inducible degradation of AOX proteins in mitochondria from appendices of A. maculatum. Image courtesy of Kikukatsu Ito.
Review Article|
September 23 2020
Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery
Tongyin Zheng;
Tongyin Zheng
*
1Department of Chemistry, Syracuse University, Syracuse, NY 13244, U.S.A.
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Yiran Yang;
Yiran Yang
*
1Department of Chemistry, Syracuse University, Syracuse, NY 13244, U.S.A.
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Carlos A. Castañeda
1Department of Chemistry, Syracuse University, Syracuse, NY 13244, U.S.A.
2Departments of Biology and Chemistry, Syracuse University, Syracuse, NY 13244, U.S.A.
3Bioinspired Institute, and the Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY 13244, U.S.A.
Correspondence: Carlos A. Castañeda (cacastan@syr.edu)
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Publisher: Portland Press Ltd
Received:
June 30 2020
Revision Received:
August 23 2020
Accepted:
August 26 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (18): 3471–3497.
Article history
Received:
June 30 2020
Revision Received:
August 23 2020
Accepted:
August 26 2020
Citation
Tongyin Zheng, Yiran Yang, Carlos A. Castañeda; Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery. Biochem J 30 September 2020; 477 (18): 3471–3497. doi: https://doi.org/10.1042/BCJ20190497
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