How Do J-Proteins Get Hsp70 to Do So Many Different Things?

Craig, Elizabeth A.; Marszałek, Jarosław

doi:10.1016/j.tibs.2017.02.007

Cited by 173 publications

(199 citation statements)

References 79 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…Indeed, analysis of human DNAJC10 shows that it interacts with signaling molecules that are important in developmental processes, including EGF, TGF‐β, and Notch (Oka et al, ), which have an integral role in morphogenesis. It has been suggested that DNAJB11, DNAJC3, and DNAJB9 can also bind a variety of unfolded and/or misfolded proteins (Craig & Marszalek, ) but the extent of binding remains elusive. Knockdown of SEC63/ dnj‐29 showed a marked increase in variance, which might be due to the large number of interactions it might have as a translocon, a protein complex associated with translocation of polypeptide across membranes.…”

Section: Discussionmentioning

confidence: 99%

DnaJ chaperones contribute to canalization

et al. 2019

View full text Add to dashboard Cite

Canalization, an intrinsic robustness of development to external (environmental) or internal (genetic) perturbations, was first proposed over half a century ago. However, whether the robustness to environmental stress (environmental canalization [EC]) and to genetic variation (genetic canalization) are underpinned by the same molecular basis remains elusive. The recent discovery of the involvement of two endoplasmic reticulum (ER)‐associated DnaJ genes in developmental buffering, orthologues of which are conserved across Metazoa, indicates that the role of ER‐associated DnaJ genes might be conserved across the animal kingdom. To test this, we surveyed the ER‐associated DnaJ chaperones in the nematode Caenorhabditis elegans. We then quantified the phenotype, in the form of variance and mean of seam cell counts, from RNA interference knockdown of DnaJs under three different temperatures. We find that seven out of eight ER‐associated DnaJs are involved in either EC or microenvironmental canalization. Moreover, we also found two DnaJ genes not specifically associated with ER (DNAJC2/dnj‐11 and DNAJA2/dnj‐19) were involved in canalization. Protein expression pattern showed that these DnaJs are upregulated by heat stress, yet not all of them are expressed in the seam cells. Moreover, we found that most of the buffering DnaJs also control lifespan. We therefore concluded that a number of DnaJ chaperones, not limited to those associated with the ER, are involved in canalization as a part of the complex system that underlies development.

show abstract

Section: Discussionmentioning

confidence: 99%

DnaJ chaperones contribute to canalization

et al. 2019

View full text Add to dashboard Cite

show abstract

“…2A). Like many other J-proteins, Hsc20 interacts with substrate protein independently from its Hsp70 partner (Craig & Marszalek, 2017). Yet, the specificity of this interaction is quite unique, with Isu and Hsc20 forming a large binding interface.…”

Section: Hsc20–isu Interactionmentioning

confidence: 99%

“…Other domains of J-proteins are highly variable, in many cases displaying no sequence or structure similarities. Many J-proteins have a J-domain at their N-terminus followed by different types of domains that bind substrates, which allow them to interact with particular substrate proteins on their own, and as consequence to target substrate for Hsp70 binding (Craig & Marszalek, 2017). While J-proteins are obligatory, they only modestly stimulate Hsp70’s ATPase activity.…”

Section: Introductionmentioning

confidence: 99%

Fe–S Cluster Hsp70 Chaperones: The ATPase Cycle and Protein Interactions

Dutkiewicz

Nowak

Craig

et al. 2017

Methods in Enzymology

Self Cite

View full text Add to dashboard Cite

Hsp70 chaperones and their obligatory J-protein cochaperones function together in many cellular processes. Via cycles of binding to short stretches of exposed amino acids on substrate proteins, Hsp70/J-protein chaperones not only facilitate protein folding but also drive intracellular protein transport, biogenesis of cellular structures, and disassembly of protein complexes. The biogenesis of iron–sulfur (Fe–S) clusters is one of the critical cellular processes that require Hsp70/J-protein action. Fe–S clusters are ubiquitous cofactors critical for activity of proteins performing diverse functions in, for example, metabolism, RNA/DNA transactions, and environmental sensing. This biogenesis process can be divided into two sequential steps: first, the assembly of an Fe–S cluster on a conserved scaffold protein, and second, the transfer of the cluster from the scaffold to a recipient protein. The second step involves Hsp70/J-protein chaperones. Via binding to the scaffold, chaperones enable cluster transfer to recipient proteins. In eukaryotic cells mitochondria have a key role in Fe–S cluster biogenesis. In this review, we focus on methods that enabled us to dissect protein interactions critical for the function of Hsp70/J-protein chaperones in the mitochondrial process of Fe–S cluster bio-genesis in the yeast Saccharomyces cerevisiae.

show abstract

“…Hsp70 and Hsp90 chaperone systems play a role in different organelles of the eukaryotic cell and regulate a wide range of events including folding of de novo synthesized polypeptides, refolding, or degradation of misfolded proteins. Furthermore, they also show disaggregation activity, facilitate protein translocation through membranes and they are involved in remodeling of multimeric protein complexes . Hsp90 is also involved in regulation of receptor‐ligand binding or assembly of protein complexes, and has been implicated in regulatory pathways such as DNA repair or immune response .…”

Section: The Chaperone Networkmentioning

confidence: 99%

Repair or destruction—an intimate liaison between ubiquitin ligases and molecular chaperones in proteostasis

2017

View full text Add to dashboard Cite

Cellular differentiation, developmental processes, and environmental factors challenge the integrity of the proteome in every eukaryotic cell. The maintenance of protein homeostasis, or proteostasis, involves folding and degradation of damaged proteins, and is essential for cellular function, organismal growth, and viability 1, 2. Misfolded proteins that cannot be refolded by chaperone machineries are degraded by specialized proteolytic systems. A major degradation pathway regulating cellular proteostasis is the ubiquitin (Ub)/proteasome system (UPS), which regulates turnover of damaged proteins that accumulate upon stress and during aging. Despite a large number of structurally unrelated substrates, Ub conjugation is remarkably selective. Substrate selectivity is mainly provided by the group of E3 enzymes. Several observations indicate that numerous E3 Ub ligases intimately collaborate with molecular chaperones to maintain the cellular proteome. In this review, we provide an overview of specialized quality control E3 ligases playing a critical role in the degradation of damaged proteins. The process of substrate recognition and turnover, the type of chaperones they team up with, and the potential pathogeneses associated with their malfunction will be further discussed.

show abstract

How Do J-Proteins Get Hsp70 to Do So Many Different Things?

Cited by 173 publications

References 79 publications

DnaJ chaperones contribute to canalization

DnaJ chaperones contribute to canalization

Fe–S Cluster Hsp70 Chaperones: The ATPase Cycle and Protein Interactions

Repair or destruction—an intimate liaison between ubiquitin ligases and molecular chaperones in proteostasis

Contact Info

Product

Resources

About