Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein

Hartl, F. Ulrich; Hayer‐Hartl, Manajit

doi:10.1126/science.1068408

Cited by 3,073 publications

(2,410 citation statements)

References 84 publications

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“…[19]). Our pathway-focused array contains sequences encoding five of the eight subunits that make up the chaperonin-containing TCP-1 protein (CCT).…”

Section: Chaperonin Subunits Are Upregulated In the Pfc But Downregulmentioning

confidence: 99%

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Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain

Kane

Konu

Jennie

et al. 2004

Molecular Brain Research

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Previously, we used cDNA microarrays to demonstrate that the phosphatidylinositol and MAP kinase signaling pathways are regulated by nicotine in different rat brain regions. In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitinconjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). In particular, relative to saline controls, ubiquitins B and C were upregulated by 33% and 47% ( Pb0.01), respectively, in the PFC. The proteasome beta subunit 1 (PSMB1) and 26S ATPase 3 (PSMC3) genes were upregulated in the PFC by 95% and 119% ( Pb0.001), respectively. In addition to the protein degradation pathway of the ubiquitin-proteasome complexes, we observed in the PFC an increase in the expression of small, ubiquitin-related modifiers (SUMO) 1 and 2 by 80% and 33%, respectively ( Pb0.001), and in 3 of 6 CCT subunits by up to 150% ( Pb0.0001). To a lesser extent, a change in the opposite direction was obtained in the expression of the same gene families in the MBH. Quantitative real-time RT-PCR was used to validate the microarray results obtained with some representative genes involved in these pathways. Taken together, our results suggest that, in response to systemic nicotine administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide an intricate control mechanism to maintain cellular homeostasis, possibly by regulating the composition and signaling of target neurons in a region-specific manner. D

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“…[19]). Our pathway-focused array contains sequences encoding five of the eight subunits that make up the chaperonin-containing TCP-1 protein (CCT).…”

Section: Chaperonin Subunits Are Upregulated In the Pfc But Downregulmentioning

confidence: 99%

“…The chaperonin-containing TCP-1 (CCT) is a subclass of the chaperonin protein family that aids in the folding of large nonnative proteins [19,31]. For example, CCT has a hetero-oligomeric structure that helps to create the correct 3-D structure of cytoskeletal proteins such as actin, tubulin and other polypeptides in the cytosol [51].…”

Section: Introductionmentioning

confidence: 99%

Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain

Kane

Konu

Jennie

et al. 2004

Molecular Brain Research

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“…Molecular chaperones, historically known as heat shock proteins, play important roles in the cellular stress response, also contributing to cellular protein homeostasis under normal conditions through a variety of mechanisms 1, 2, 3, 4. Chaperone activity is underlined by their ability to form interactions with client proteins, as well as other proteins, e.g.…”

Section: Introductionmentioning

confidence: 99%

Quantitative proteomics and network analysis of SSA1 and SSB1 deletion mutants reveals robustness of chaperone HSP70 network in Saccharomyces cerevisiae

Jarnuczak¹,

Eyers

Schwartz³

et al. 2015

Proteomics

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Molecular chaperones play an important role in protein homeostasis and the cellular response to stress. In particular, the HSP70 chaperones in yeast mediate a large volume of protein folding through transient associations with their substrates. This chaperone interaction network can be disturbed by various perturbations, such as environmental stress or a gene deletion. Here, we consider deletions of two major chaperone proteins, SSA1 and SSB1, from the chaperone network in Sacchromyces cerevisiae. We employ a SILAC‐based approach to examine changes in global and local protein abundance and rationalise our results via network analysis and graph theoretical approaches. Although the deletions result in an overall increase in intracellular protein content, correlated with an increase in cell size, this is not matched by substantial changes in individual protein concentrations. Despite the phenotypic robustness to deletion of these major hub proteins, it cannot be simply explained by the presence of paralogues. Instead, network analysis and a theoretical consideration of folding workload suggest that the robustness to perturbation is a product of the overall network structure. This highlights how quantitative proteomics and systems modelling can be used to rationalise emergent network properties, and how the HSP70 system can accommodate the loss of major hubs.

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“…1,2 Molecular chaperones are also important in regulating the balance between protein synthesis and degradation. 1,2 HSPs have been identified in diverse organisms, ranging from bacteria to humans, and are classified on the basis of their molecular weight. 3,4 The four major groups include HSP110, HSP90, HSP70 and HSP27.…”

mentioning

confidence: 99%

“…HSP90 is ubiquitously expressed in the cytoplasm of normal cells where it binds with many client proteins and is involved in homeostasis. [1][2][3][4][5][6][7] In normal cells, HSP90 is expressed at relatively low levels and does not form complexes with other chaperone proteins. 8 Thus, others have suggested that HSP90 is present in latent form in normal cells.…”

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confidence: 99%

Expression of heat-shock protein-90 in non-Hodgkin's lymphomas

et al. 2005

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Heat-shock protein-90 (HSP90) inhibitors are currently being used in phase I clinical trials for treating patients with a variety of neoplasms including lymphomas. Using immunohistochemical methods, we assessed for HSP90 expression in 412 cases of non-Hodgkin's lymphoma. In B-cell lymphomas, HSP90 was moderately to strongly expressed in all cases of Burkitt's lymphoma (5/5, 100%), and in subsets of follicular lymphoma (17/28, 61%), diffuse large B-cell lymphoma (27/46, 59%), nodal marginal zone B-cell lymphoma (6/16, 38%), plasma cell neoplasms (14/39, 36%), small lymphocytic lymphoma/chronic lymphocytic leukemia (3/9, 33%), mantle cell lymphoma (12/38, 32%) and lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (3/10, 30%). HSP90 was weakly expressed in six of 14 (43%) cases of extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue. In T-cell lymphomas, HSP90 was moderately to strongly expressed in subsets of anaplastic large-cell lymphoma (14/24, 58%; 9/12 ALK þ and 5/12 ALKÀ), precursor-T-cell lymphoblastic leukemia/lymphoma (20/65, 31%), unspecified peripheral T-cell lymphoma (8/43, 23%) and angioimmunoblastic T-cell lymphoma (2/17, 12%). HSP90 was weakly expressed in seven of 58 (12%) cases of mycosis fungoides. We conclude that HSP90 is commonly expressed in a subset of many types of B-and T-cell lymphoma. These data suggest that many lymphoma types are suitable targets for modulation of HSP90 activity, and that HSP90 inhibitors are a potential investigational therapy for lymphoma patients.

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Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein

Cited by 3,073 publications

References 84 publications

Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain

Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain

Quantitative proteomics and network analysis of SSA1 and SSB1 deletion mutants reveals robustness of chaperone HSP70 network in Saccharomyces cerevisiae

Expression of heat-shock protein-90 in non-Hodgkin's lymphomas

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