A comprehensive analysis of prefoldins and their implication in cancer

Abstract

Summary Prefoldins (PFDNs) are evolutionary conserved co-chaperones, initially discovered in archaea but universally present in eukaryotes. PFDNs are prevalently organized into hetero-hexameric complexes. Although they have been overlooked since their discovery and their functions remain elusive, several reports indicate they act as co-chaperones escorting misfolded or non-native proteins to group II chaperonins. Unlike the eukaryotic PFDNs which interact with cytoskeletal components, the archaeal PFDNs can bind and stabilize a wide range of substrates, possibly due to their great structural diversity. The discovery of the unconventional RPB5 interactor (URI) PFDN-like complex (UPC) suggests that PFDNs have versatile functions and are required for different cellular processes, including an important role in cancer. Here, we summarize their functions across different species. Moreover, a comprehensive analysis of PFDNs genomic alterations across cancer types by using large-scale cancer genomic data indicates that PFDNs are a new class of non-mutated proteins significantly overexpressed in some cancer types.

Prefoldin Function in Cellular Protein Homeostasis and Human Diseases

“…Table 1 summarizes the identified interactors with different prefoldin subunits. A recent review described links between interactors of prefoldin subunits and the progression of cancer ( Liang et al, 2020 ; Herranz-Montoya et al, 2021 ). The sections below focus on the involvement of prefoldin subunits in transcription, protein aggregation, and degradation.…”

“…Cancer refers to a group of disorders that are caused by the uncontrolled division of cells that may start in every organ of the body and, in severe cases, spread to other organs ( Hausman, 2019 ). Several studies reported the contribution of the prefoldin complex and its subunits to the onset and progression of some cancers ( Table 2 ) ( Liang et al, 2020 ; Herranz-Montoya et al, 2021 ). Higher prefoldin expression was observed in cancer cell lines compared with non-cancerous cells ( Boudiaf-Benmammar et al, 2013 ).…”

A Comprehensive Enumeration of the Human Proteostasis Network. 1. Components of Translation, Protein Folding, and Organelle-Specific Systems

“…Ribosome (Khatter et al, 2015) Ribosome biogenesis (Ameismeier et al, 2018;Bohnsack and Bohnsack, 2019;Liang et al, 2020) Translation initiation (Jackson et al, 2010) Translation elongation (Antonellis and Green, 2008;Dever et al, 2018) Translation termination (Hellen, 2018) Ribosomal quality control (Brandman and Hegde, 2016;Duttler et al, 2013;Joazeiro, 2019) Chaperones and folding enzymes General (Brehme et al, 2014;Jayaraj et al, 2020;Shemesh et al, 2021) HSP70 system (Bracher and Verghese, 2015;Brocchieri et al, 2008;Kampinga and Craig, 2010;Mayer and Gierasch, 2019;Rosenzweig et al, 2019) HSP90 system (Pearl, 2016;Schopf et al, 2017;Taipale et al, 2014) TRiC/CCT system (Gestaut et al, 2019;Herranz-Montoya et al, 2021;Mukherjee et al, 2010;Tian and Cowan, 2013;Willardson and Howlett, 2007) sHSP (Boncoraglio et al, 2012;Garrido et al, 2012;Reinle et al, 2022) PDI (Galligan and Petersen, 2012) PPIase (Pemberton and Kay, 2005)…”

The prefoldin‐like protein AtURI exhibits characteristics of intrinsically disordered proteins

“…Animal and yeast models show that prefoldin-like proteins are regulators of cell survival and proliferation in response to environmental and nutrient stress [1]. Prefoldin-like proteins were identified in several independent studies in animals and yeast.…”

“…URI is unique among prefoldin and prefoldin-like proteins in that it is a larger protein. In addition to its involvement in several cellular functions related to its role as a cochaperone, either as part of the PFDL complex or as an independent subunit, its role as a signaling protein has also been described [1]. In yeast, URI/Bud27 is involved in transcription indirectly by assembling the three nuclear RNA polymerases in the cytoplasm [11] and directly by modulating their transcriptional activity in close association with the chromatin remodeler RSC [12][13][14][15].…”