Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains

Piette, Benjamin L.; Alerasool, Nader; Lin, Zhen Yuan; Lacoste, Jessica; Lam, Mandy Hiu Yi; Qian, Wesley Wei; Tran, Stephanie; Larsen, Brett; Campos, Eric I.; Peng, Jian; Gingras, Anne Claude; Taipale, Mikko

doi:10.1016/j.molcel.2021.04.012

Cited by 58 publications

(62 citation statements)

References 121 publications

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“…This is in line with the increased protein aggregation and decreased molecular chaperones in Rpl39l –/– mice, including DNAJB6/8 and mitochondria-specific DNAJC30 ( Gillis et al., 2013 ; Tebbenkamp et al., 2018 ). It was recently shown that the DNAJ family of HSP40 co-chaperones recognize substrates in cell-type specific manner ( Piette et al., 2021 ; Thiruvalluvan et al., 2020 ), reminiscent of our findings that DNAJB6 presents in pre-meiotic cells and DNAJB8 is mainly expressed in post-meiotic cells. The decreased protein ubiquitination further supports the notion of aberrant PQC in the absence of RPL39L ( An and Harper, 2020 ; Inada, 2017 ; Sung et al., 2016 ; Takehara et al., 2021 ).…”

Section: Discussionsupporting

confidence: 86%

Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis

et al. 2021

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Section: Discussionsupporting

confidence: 86%

Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis

et al. 2021

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“…Taking the data together, we propose a model in which CMA is a key component of the quality control of newly synthesized histones H3 and H4 and the balance between a network of chaperones and their different outcome is key for understanding how cells cope with defective newly synthesized histones H3 and H4 (Figure 6G ). Recent reports showed that the chaperone DNAJC9 binds to histones H3 and H4 and recruits heat shock chaperones to fold histone dimers during the maturation cascade of newly synthesized histones and at the time of their deposition into chromatin ( 10 , 31 ). Considering our results, we hypothesized that if the folding activity mediated by the heat shock proteins network fails, defective newly synthesized histones H3 and H4 are degraded by CMA.…”

Section: Discussionmentioning

confidence: 99%

Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control

Hormazábal

Saavedra

Espinoza-Arratia

et al. 2022

Nucleic Acids Research

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Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.

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“…Based on co-immunoprecipitation in macrophage membrane fractions, it was shown that DnaJ homolog subfamily C member 1 (Dnajc1, also called MTJ-1) interacts with GRP78 at the cell membrane and enables cell-surface localization of GRP78 ( 97 ). Dnajc1 belongs to the family of J domain proteins (JDPs) which bind and activate Hsp70 proteins through their J domain ( 98 ). The interaction of GRP78 with Dnajc1 might thus explain the association of GRP78 with cell membranes.…”

Section: The Endocytic and Signaling Receptorsmentioning

confidence: 99%

Alpha-2-Macroglobulin in Inflammation, Immunity and Infections

2021

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Alpha-2-macroglobulin is an extracellular macromolecule mainly known for its role as a broad-spectrum protease inhibitor. By presenting itself as an optimal substrate for endopeptidases of all catalytic types, alpha-2-macroglobulin lures active proteases into its molecular cage and subsequently ‘flags’ their complex for elimination. In addition to its role as a regulator of extracellular proteolysis, alpha-2-macroglobulin also has other functions such as switching proteolysis towards small substrates, facilitating cell migration and the binding of cytokines, growth factors and damaged extracellular proteins. These functions appear particularly important in the context of immune-cell function. In this review manuscript, we provide an overview of all functions of alpha-2-macroglobulin and place these in the context of inflammation, immunity and infections.

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Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains

Cited by 58 publications

References 121 publications

Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis

Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis

Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control

Alpha-2-Macroglobulin in Inflammation, Immunity and Infections

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