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1.
Nat Methods ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886577

ABSTRACT

In a human cell, thousands of replication forks simultaneously coordinate duplication of the entire genome. The rate at which this process occurs might depend on the epigenetic state of the genome and vary between, or even within, cell types. To accurately measure DNA replication speeds, we developed single-cell 5-ethynyl-2'-deoxyuridine sequencing to detect nascent replicated DNA. We observed that the DNA replication speed is not constant but increases during S phase of the cell cycle. Using genetic and pharmacological perturbations we were able to alter this acceleration of replication and conclude that DNA damage inflicted by the process of transcription limits the speed of replication during early S phase. In late S phase, during which less-transcribed regions replicate, replication accelerates and approaches its maximum speed.

2.
Sci Signal ; 16(782): eabp8923, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37098120

ABSTRACT

DDX RNA helicases promote RNA processing, but DDX3X also activates casein kinase 1 (CK1ε). We show that other DDX proteins also stimulate the protein kinase activity of CK1ε and that this extends to casein kinase 2 (CK2). CK2 enzymatic activity was stimulated by various DDX proteins at high substrate concentrations. DDX1, DDX24, DDX41, and DDX54 were required for full kinase activity in vitro and in Xenopus embryos. Mutational analysis of DDX3X indicated that CK1 and CK2 kinase stimulation engages its RNA binding but not catalytic motifs. Mathematical modeling of enzyme kinetics and stopped-flow spectroscopy showed that DDX proteins function as nucleotide exchange factors toward CK2 and reduce unproductive reaction intermediates and substrate inhibition. Our study reveals protein kinase stimulation by nucleotide exchange as important for kinase regulation and as a generic function of DDX proteins.


Subject(s)
Casein Kinase II , DEAD-box RNA Helicases , Nucleotides , Xenopus , Xenopus Proteins/metabolism , DEAD-box RNA Helicases/metabolism , Casein Kinase II/metabolism , Nucleotides/metabolism , RNA Processing, Post-Transcriptional , HEK293 Cells , Humans , Models, Theoretical , HeLa Cells , Embryo, Nonmammalian
3.
Trends Cell Biol ; 32(12): 1035-1048, 2022 12.
Article in English | MEDLINE | ID: mdl-35717422

ABSTRACT

Wnt signalling is an essential player in tissue formation, notably in the regulation of stem cell function. Wnt signalling is best known for its roles in G1/S progression. However, a complex Wnt programme that also mediates mitotic progression and asymmetric cell division (ACD) is emerging. Recent developments in this area have provided mechanistic insights as well as tools to engineer or target Wnt signalling for translational and therapeutic purposes. Here, we discuss the bidirectional relationship between Wnt activity and mitosis. We emphasise how various Wnt-dependent mechanisms control spindle dynamics, chromosome segregation, and ACD. Finally, we illustrate how knowledge about these mechanisms has been successfully employed in tissue engineering for regenerative medicine applications.


Subject(s)
Tissue Engineering , Wnt Signaling Pathway , Humans , Mitosis , Chromosome Segregation , Asymmetric Cell Division , Spindle Apparatus/physiology
4.
Proc Natl Acad Sci U S A ; 118(34)2021 08 24.
Article in English | MEDLINE | ID: mdl-34417301

ABSTRACT

Canonical Wnt signaling plays critical roles in development and tissue renewal by regulating ß-catenin target genes. Recent evidence showed that ß-catenin-independent Wnt signaling is also required for faithful execution of mitosis. However, the targets and specific functions of mitotic Wnt signaling still remain uncharacterized. Using phosphoproteomics, we identified that Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis. We found that Dishevelled recruits KIF2A via its N-terminal and motor domains, which is further promoted upon LRP6 signalosome formation during cell division. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization at the spindle. Accordingly, inhibition of basal Wnt signaling leads to chromosome misalignment in somatic cells and pluripotent stem cells. We propose that Wnt signaling monitors KIF2A activity at the spindle poles during mitosis to ensure timely chromosome alignment. Our findings highlight a function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.


Subject(s)
Chromosome Segregation , Chromosomes, Human/genetics , Kinesins/metabolism , Mitosis , Spindle Apparatus/physiology , Wnt Signaling Pathway , Chromosome Positioning , Humans , Kinesins/genetics
5.
EMBO Rep ; 22(5): e51415, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33786993

ABSTRACT

The tumour suppressors RNF43 and ZNRF3 play a central role in development and tissue homeostasis by promoting the turnover of the Wnt receptors LRP6 and Frizzled (FZD). The stem cell growth factor R-spondin induces auto-ubiquitination and membrane clearance of ZNRF3/RNF43 to promote Wnt signalling. However, the deubiquitinase stabilising ZNRF3/RNF43 at the plasma membrane remains unknown. Here, we show that the USP42 antagonises R-spondin by protecting ZNRF3/RNF43 from ubiquitin-dependent clearance. USP42 binds to the Dishevelled interacting region (DIR) of ZNRF3 and stalls the R-spondin-LGR4-ZNRF3 ternary complex by deubiquitinating ZNRF3. Accordingly, USP42 increases the turnover of LRP6 and Frizzled (FZD) receptors and inhibits Wnt signalling. Furthermore, we show that USP42 functions as a roadblock for paracrine Wnt signalling in colon cancer cells and mouse small intestinal organoids. We provide new mechanistic insights into the regulation R-spondin and conclude that USP42 is crucial for ZNRF3/RNF43 stabilisation at the cell surface.


Subject(s)
Thrombospondins , Ubiquitin-Protein Ligases , Animals , Mice , Receptors, G-Protein-Coupled/genetics , Thrombospondins/genetics , Thrombospondins/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitination , Wnt Signaling Pathway
6.
Mol Cell Oncol ; 8(6): 2011564, 2021.
Article in English | MEDLINE | ID: mdl-35419471

ABSTRACT

WNT signaling regulates cell cycle progression and fate determination through ß-catenin dependent transcription, and its misregulation is often associated with tumorigenesis. Our recent work demonstrated that basal WNT activity is also required to ensure proper chromosome alignment during mitosis through the regulation of kinesin family member 2A (KIF2A).

7.
Life Sci Alliance ; 4(1)2021 01.
Article in English | MEDLINE | ID: mdl-33257473

ABSTRACT

Wnt signaling is crucial for proper development, tissue homeostasis and cell cycle regulation. A key role of Wnt signaling is the GSK3ß-mediated stabilization of ß-catenin, which mediates many of the critical roles of Wnt signaling. In addition, it was recently revealed that Wnt signaling can also act independently of ß-catenin. In fact, Wnt mediated stabilization of proteins (Wnt/STOP) that involves an LRP6-DVL-dependent signaling cascade is required for proper regulation of mitosis and for faithful chromosome segregation in human somatic cells. We show that inhibition of Wnt/LRP6 signaling causes whole chromosome missegregation and aneuploidy by triggering abnormally increased microtubule growth rates in mitotic spindles, and this is mediated by increased GSK3ß activity. We demonstrate that proper mitosis and maintenance of numerical chromosome stability requires continuous basal autocrine Wnt signaling that involves secretion of Wnts. Importantly, we identified Wnt10b as a Wnt ligand required for the maintenance of normal mitotic microtubule dynamics and for proper chromosome segregation. Thus, a self-maintaining Wnt10b-GSK3ß-driven cellular machinery ensures the proper execution of mitosis and karyotype stability in human somatic cells.


Subject(s)
Aneuploidy , Dishevelled Proteins/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Proto-Oncogene Proteins/metabolism , Wnt Proteins/metabolism , Wnt Signaling Pathway/genetics , beta Catenin/metabolism , Chromosomal Instability/drug effects , Chromosomal Instability/genetics , Chromosome Segregation/drug effects , Chromosome Segregation/genetics , Gene Silencing , HCT116 Cells , Humans , Intercellular Signaling Peptides and Proteins/pharmacology , Intracellular Signaling Peptides and Proteins/deficiency , Intracellular Signaling Peptides and Proteins/genetics , Microtubules/metabolism , Mitosis/drug effects , Mitosis/genetics , Protein Stability , Proto-Oncogene Proteins/genetics , Receptors, G-Protein-Coupled/deficiency , Receptors, G-Protein-Coupled/genetics , Spindle Apparatus/metabolism , Transfection , Wnt Proteins/genetics , Wnt Signaling Pathway/drug effects
8.
EMBO Rep ; 18(5): 712-725, 2017 05.
Article in English | MEDLINE | ID: mdl-28341812

ABSTRACT

Wnt/ß-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky ß-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/ß-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis. We conclude that GPR37 is crucial for cellular protein quality control during Wnt signaling.


Subject(s)
Endoplasmic Reticulum/metabolism , Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Molecular Chaperones/metabolism , Parkinson Disease/metabolism , Receptors, G-Protein-Coupled/metabolism , Wnt Signaling Pathway , Animals , Endoplasmic Reticulum-Associated Degradation , Low Density Lipoprotein Receptor-Related Protein-6/genetics , Mice , Neural Stem Cells/metabolism , Phosphorylation , Proteolysis , Receptors, G-Protein-Coupled/genetics , Signal Transduction , Wnt Proteins/genetics , Wnt Proteins/metabolism
9.
Trends Cell Biol ; 26(12): 956-967, 2016 12.
Article in English | MEDLINE | ID: mdl-27568239

ABSTRACT

Wnt/LRP6 signaling is best known for the ß-catenin-dependent regulation of target genes. However, pathway branches have recently emerged, including Wnt/STOP signaling, which act independently of ß-catenin and transcription. We review here the molecular mechanisms underlying ß-catenin-independent Wnt/LRP6 signaling cascades and their implications for cell biology, development, and physiology.


Subject(s)
Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Wnt Signaling Pathway , beta Catenin/metabolism , Animals , Humans , Models, Biological , Protein Stability , Receptor Cross-Talk
10.
Cell ; 163(5): 1225-1236, 2015 Nov 19.
Article in English | MEDLINE | ID: mdl-26590424

ABSTRACT

The canonical Wnt signaling pathway is of paramount importance in development and disease. An emergent question is whether the upstream cascade of the canonical Wnt pathway has physiologically relevant roles beyond ß-catenin-mediated transcription, which is difficult to study due to the pervasive role of this protein. Here, we show that transcriptionally silent spermatozoa respond to Wnt signals released from the epididymis and that mice mutant for the Wnt regulator Cyclin Y-like 1 are male sterile due to immotile and malformed spermatozoa. Post-transcriptional Wnt signaling impacts spermatozoa through GSK3 by (1) reducing global protein poly-ubiquitination to maintain protein homeostasis; (2) inhibiting septin 4 phosphorylation to establish a membrane diffusion barrier in the sperm tail; and (3) inhibiting protein phosphatase 1 to initiate sperm motility. The results indicate that Wnt signaling orchestrates a rich post-transcriptional sperm maturation program and invite revisiting transcription-independent Wnt signaling in somatic cells as well.


Subject(s)
Epididymis/metabolism , Gene Expression Regulation , Sperm Maturation , Wnt Signaling Pathway , Animals , Axin Protein/metabolism , Cyclins/metabolism , Glycogen Synthase Kinase 3/metabolism , Male , Mice , Phosphorylation , Protein Processing, Post-Translational , RNA Processing, Post-Transcriptional , Septins/metabolism
11.
Proc Natl Acad Sci U S A ; 112(18): 5732-7, 2015 May 05.
Article in English | MEDLINE | ID: mdl-25901317

ABSTRACT

During Xenopus development, Wnt signaling is thought to function first after midblastula transition to regulate axial patterning via ß-catenin-mediated transcription. Here, we report that Wnt/glycogen synthase kinase 3 (GSK3) signaling functions posttranscriptionally already in mature oocytes via Wnt/stabilization of proteins (STOP) signaling. Wnt signaling is induced in oocytes after their entry into meiotic metaphase II and declines again upon exit into interphase. Wnt signaling inhibits Gsk3 and thereby protects proteins from polyubiquitination and degradation in mature oocytes. In a protein array screen, we identify a cluster of mitotic effector proteins that are polyubiquitinated in a Gsk3-dependent manner in Xenopus. Consequently inhibition of maternal Wnt/STOP signaling, but not ß-catenin signaling, leads to early cleavage arrest after fertilization. The results support a novel role for Wnt signaling in cell cycle progression independent of ß-catenin.


Subject(s)
Gene Expression Regulation, Developmental , Glycogen Synthase Kinase 3/metabolism , Wnt1 Protein/metabolism , Xenopus Proteins/metabolism , Xenopus laevis/embryology , Animals , Cell Cycle , Fertilization , Glycogen Synthase Kinase 3 beta , Humans , Mitosis , Oocytes/cytology , Protein Array Analysis , Signal Transduction , Transcription, Genetic
12.
Mol Cell ; 54(4): 663-74, 2014 May 22.
Article in English | MEDLINE | ID: mdl-24837680

ABSTRACT

Canonical Wnt signaling is thought to regulate cell behavior mainly by inducing ß-catenin-dependent transcription of target genes. In proliferating cells Wnt signaling peaks in the G2/M phase of the cell cycle, but the significance of this "mitotic Wnt signaling" is unclear. Here we introduce Wnt-dependent stabilization of proteins (Wnt/STOP), which is independent of ß-catenin and peaks during mitosis. We show that Wnt/STOP plays a critical role in protecting proteins, including c-MYC, from GSK3-dependent polyubiquitination and degradation. Wnt/STOP signaling increases cellular protein levels and cell size. Wnt/STOP, rather than ß-catenin signaling, is the dominant mode of Wnt signaling in several cancer cell lines, where it is required for cell growth. We propose that Wnt/STOP signaling slows down protein degradation as cells prepare to divide.


Subject(s)
Cell Size , Mitosis , Wnt Proteins/metabolism , Wnt Signaling Pathway , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation , Glycogen Synthase Kinase 3/metabolism , HEK293 Cells , HeLa Cells , Humans , Protein Array Analysis , Protein Stability , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Ubiquitination , Wnt Proteins/genetics
13.
Nature ; 487(7405): 38, 2012 Jul 04.
Article in English | MEDLINE | ID: mdl-22763537
14.
EMBO J ; 31(12): 2705-13, 2012 Jun 13.
Article in English | MEDLINE | ID: mdl-22617425

ABSTRACT

Canonical Wnt signalling plays an important role in development, tissue homeostasis, and cancer. At the cellular level, canonical Wnt signalling acts by regulating cell fate, cell growth, and cell proliferation. With regard to proliferation, there is increasing evidence for a complex interaction between canonical Wnt signalling and the cell cycle. Mitogenic Wnt signalling regulates cell proliferation by promoting G1 phase. In mitosis, components of the Wnt signalling cascade function directly in spindle formation. Moreover, Wnt signalling is strongly activated in mitosis, suggesting that 'mitotic Wnt signalling' plays an important role to orchestrate a cell division program. Here, we review the complex interplay between Wnt signalling and the cell cycle.


Subject(s)
Cell Proliferation , Gene Expression Regulation , Mitosis , Wnt Proteins/metabolism , Wnt Signaling Pathway , Animals , Cell Differentiation , Humans , Models, Biological , Neoplasms/metabolism
15.
J Mol Biol ; 421(2-3): 270-81, 2012 Aug 10.
Article in English | MEDLINE | ID: mdl-22200483

ABSTRACT

The formation of aggregates by misfolded proteins is thought to be inherently toxic, affecting cell fitness. This observation has led to the suggestion that selection against protein aggregation might be a major constraint on protein evolution. The precise fitness cost associated with protein aggregation has been traditionally difficult to evaluate. Moreover, it is not known if the detrimental effect of aggregates on cell physiology is generic or depends on the specific structural features of the protein deposit. In bacteria, the accumulation of intracellular protein aggregates reduces cell reproductive ability, promoting cellular aging. Here, we exploit the cell division defects promoted by the intracellular aggregation of Alzheimer's-disease-related amyloid ß peptide in bacteria to demonstrate that the fitness cost associated with protein misfolding and aggregation is connected to the protein sequence, which controls both the in vivo aggregation rates and the conformational properties of the aggregates. We also show that the deleterious impact of protein aggregation on bacterial division can be buffered by molecular chaperones, likely broadening the sequential space on which natural selection can act. Overall, the results in the present work have potential implications for the evolution of proteins and provide a robust system to experimentally model and quantify the impact of protein aggregation on cell fitness.


Subject(s)
Amyloid/chemistry , Bacteria/chemistry , Peptides/chemistry , Bacterial Physiological Phenomena , Cell Division , Green Fluorescent Proteins/chemistry , Microscopy, Atomic Force , Microscopy, Confocal , Molecular Chaperones/chemistry , Protein Conformation , Solubility , Spectrometry, Fluorescence
16.
J Biol Chem ; 286(29): 25547-55, 2011 Jul 22.
Article in English | MEDLINE | ID: mdl-21642426

ABSTRACT

ClpB is a hexameric chaperone that solubilizes and reactivates protein aggregates in cooperation with the Hsp70/DnaK chaperone system. Each of the identical protein monomers contains two nucleotide binding domains (NBD), whose ATPase activity must be coupled to exert on the substrate the mechanical work required for its reactivation. However, how communication between these sites occurs is at present poorly understood. We have studied herein the affinity of each of the NBDs for nucleotides in WT ClpB and protein variants in which one or both sites are mutated to selectively impair nucleotide binding or hydrolysis. Our data show that the affinity of NBD2 for nucleotides (K(d) = 3-7 µm) is significantly higher than that of NBD1. Interestingly, the affinity of NBD1 depends on nucleotide binding to NBD2. Binding of ATP, but not ADP, to NBD2 increases the affinity of NBD1 (the K(d) decreases from ≈160-300 to 50-60 µm) for the corresponding nucleotide. Moreover, filling of the NBD2 ring with ATP allows the cooperative binding of this nucleotide and substrates to the NBD1 ring. Data also suggest that a minimum of four subunits cooperate to bind and reactivate two different aggregated protein substrates.


Subject(s)
Escherichia coli Proteins/chemistry , Escherichia coli Proteins/metabolism , Heat-Shock Proteins/chemistry , Heat-Shock Proteins/metabolism , Nucleotides/metabolism , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Allosteric Regulation , Endopeptidase Clp , Escherichia coli Proteins/genetics , Heat-Shock Proteins/genetics , Mutation , Protein Binding , Protein Structure, Tertiary , Substrate Specificity
17.
Biochemistry ; 50(12): 1991-2003, 2011 Mar 29.
Article in English | MEDLINE | ID: mdl-21309513

ABSTRACT

ClpB is a hexameric molecular chaperone that, together with the DnaK system, has the ability to disaggregate stress-denatured proteins. The hexamer is a highly dynamic complex, able to reshuffle subunits. To further characterize the biological implications of the ClpB oligomerization state, the association equilibrium of the wild-type (wt) protein and of two deletion mutants, which lack part or the whole M domain, was quantitatively analyzed under different experimental conditions, using several biophysical [analytical ultracentrifugation, composition-gradient (CG) static light scattering, and circular dichroism] and biochemical (ATPase and chaperone activity) methods. We have found that (i) ClpB self-associates from monomers to form hexamers and higher-order oligomers that have been tentatively assigned to dodecamers, (ii) oligomer dissociation is not accompanied by modifications of the protein secondary structure, (iii) the M domain is engaged in intersubunit interactions that stabilize the protein hexamer, and (iv) the nucleotide-induced rearrangement of ClpB affects the protein oligomeric core, in addition to the proposed radial extension of the M domain. The difference in the stability of the ATP- and ADP-bound states [ΔΔG(ATP-ADP) = -10 kJ/mol] might explain how nucleotide exchange promotes the conformational change of the protein particle that drives its functional cycle.


Subject(s)
Heat-Shock Proteins/chemistry , Heat-Shock Proteins/metabolism , Nucleotides/pharmacology , Protein Multimerization/drug effects , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Hydrodynamics , Models, Molecular , Protein Stability/drug effects , Protein Structure, Quaternary , Protein Structure, Tertiary , Protein Subunits/chemistry , Protein Subunits/metabolism , Thermodynamics
18.
Cell ; 143(7): 1044-6, 2010 Dec 23.
Article in English | MEDLINE | ID: mdl-21183070

ABSTRACT

Two key events in Wnt signal transduction, receptor endocytosis and inactivation of Glycogen Synthase Kinase 3 (GSK3), remain incompletely understood. Taelman et al. (2010) discover that Wnt signaling inactivates GSK3 by sequestering the enzyme in multivesicular bodies, thus linking these two events and providing a new framework for understanding Wnt signaling.

19.
Science ; 327(5964): 459-63, 2010 Jan 22.
Article in English | MEDLINE | ID: mdl-20093472

ABSTRACT

Wnt/beta-catenin signaling is important in stem cell biology, embryonic development, and disease, including cancer. However, the mechanism of Wnt signal transmission, notably how the receptors are activated, remains incompletely understood. We found that the prorenin receptor (PRR) is a component of the Wnt receptor complex. PRR functions in a renin-independent manner as an adaptor between Wnt receptors and the vacuolar H+-adenosine triphosphatase (V-ATPase) complex. Moreover, PRR and V-ATPase were required to mediate Wnt signaling during antero-posterior patterning of Xenopus early central nervous system development. The results reveal an unsuspected role for the prorenin receptor, V-ATPase activity, and acidification during Wnt/beta-catenin signaling.


Subject(s)
Receptors, Cell Surface/metabolism , Signal Transduction , Vacuolar Proton-Translocating ATPases/metabolism , Wnt Proteins/metabolism , Xenopus Proteins/metabolism , Animals , Body Patterning , Cell Line , Cell Line, Tumor , Central Nervous System/cytology , Central Nervous System/embryology , Embryo, Nonmammalian/metabolism , Frizzled Receptors/metabolism , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Hydrogen-Ion Concentration , LDL-Receptor Related Proteins/metabolism , Low Density Lipoprotein Receptor-Related Protein-6 , Mice , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Phosphorylation , RNA, Small Interfering , Receptors, Cell Surface/genetics , Vacuolar Proton-Translocating ATPases/antagonists & inhibitors , Wnt3 Protein , Xenopus/embryology , Xenopus/metabolism , Xenopus Proteins/genetics , beta Catenin/metabolism , Prorenin Receptor
20.
FEBS Lett ; 583(18): 2991-6, 2009 Sep 17.
Article in English | MEDLINE | ID: mdl-19698713

ABSTRACT

Intracellular protein aggregates formed under severe thermal stress can be reactivated by the concerted action of the Hsp70 system and Hsp100 chaperones. We analyzed here the interaction of DnaJ/DnaK and ClpB with protein aggregates. We show that aggregate properties modulate chaperone binding, which in turn determines aggregate reactivation efficiency. ClpB binding strictly depends on previous DnaK association with the aggregate. The affinity of ClpB for the aggregate-DnaK complex is low (K(d)=5-10 microM), indicating a weak interaction. Therefore, formation of the DnaK-ClpB bichaperone network is a three step process. After initial DnaJ binding, the cochaperone drives association of DnaK to aggregates, and in the third step, as shown here, DnaK mediates ClpB interaction with the aggregate surface.


Subject(s)
Escherichia coli Proteins/metabolism , HSP70 Heat-Shock Proteins/metabolism , Heat-Shock Proteins/metabolism , Molecular Chaperones/metabolism , Endopeptidase Clp , HSP40 Heat-Shock Proteins , Protein Binding
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