The small heat shock proteins αB-crystallin and Hsp27 suppress SOD1 aggregation in vitro

Yerbury, Justin J.; Gower, Dane; Vanags, Laura Z.; Roberts, Kate; Lee, Jodi A; Ecroyd, Heath

doi:10.1007/s12192-012-0371-1

Cited by 79 publications

(68 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HSP27 is a molecule with pleiotropic characteristics involved in different roles in normal and pathological cells. HSP7 stabilizes protein folding and suppress protein aggregation (37,38). Similarly, Hic-5 has been reported to function as a chaperone, regulating diverse functions such as growth and differentiation (39 -41) in a cell-or tissue-specific manner.…”

Section: Discussionmentioning

confidence: 99%

Negative Regulation of NADPH Oxidase 4 by Hydrogen Peroxide-inducible Clone 5 (Hic-5) Protein

Desai

Zhou

Estrada

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Nox4 is known to be regulated primarily at the transcriptional level and regulates myofibroblast differentiation. Results: Nox4 protein expression is suppressed by Hic-5 via Cbl-c-and HSP27-mediated ubiquitination and proteasomal degradation. Conclusion: Nox4 is posttranslationally regulated by Hic-5, and its interacting proteins, Cbl-c and HSP27 regulate myofibroblast differentiation and senescence. Significance: Prosenescence and profibrotic effects of Nox4 may be mitigated by Hic-5-mediated suppression of its protein expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Negative Regulation of NADPH Oxidase 4 by Hydrogen Peroxide-inducible Clone 5 (Hic-5) Protein

Desai

Zhou

Estrada

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Ubiquitinated Bc has also been identified by immunochemical analysis in cytoplasmic inclusions in brains of patients with multiple system atrophy [192]. More recently, it has been shown that the aggregation of SOD1, a major protein involved in the pathogenesis of ALS, is prevented by both Bc and Hsp27 [193,194] and that Hsp22, in concert with other chaperones, promotes autophagic removal of misfolded proteins in ALS [171].…”

Section: The Role Of Shsps In Neurodegenerative Diseasementioning

confidence: 99%

Small heat-shock proteins: important players in regulating cellular proteostasis

Treweek

Meehan

Ecroyd

et al. 2014

Cell. Mol. Life Sci.

Self Cite

175

177

View full text Add to dashboard Cite

Small heat-shock proteins (sHsps) are a diverse family of intra-cellular molecular chaperone proteins that play a critical role in mitigating and preventing protein aggregation under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) thereby avoiding the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. Significant progress has been made of late in understanding the structure and chaperone mechanism of sHsps. In this review, we discuss some of these advances, with a focus on mammalian sHsp hetero-oligomerisation, the mechanism by which sHsps act as molecular chaperones to prevent both amorphous and fibrillar protein aggregation, and the role of posttranslational modifications in sHsp chaperone function, particularly in the context of disease. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Abstract (word count = 159)Small heat-shock proteins (sHsps) are a diverse family of intracellular molecular chaperone proteins that play a critical role in preventing protein unfolding, misfolding and aggregation, particularly under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) and thereby avoid the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. There has been much research into the structure and mechanism of chaperone action of sHsps over approximately the past 30 years, and significant progress has been made of late, however, there are still many unanswered questions relating to these aspects of sHsps. In this review, we outline some of the recent advances in understanding the structure and function of mammalian sHsps, particularly in the context of their many and varied roles in disease.

show abstract

“…Indeed, we recently observed that the aggregation processes of TDP-43, FUS, and SOD1 in cells are distinct, and that they result in inclusions with varied characteristics (33). In particular, SOD1 aggregates, which are the most intensely studied inclusions, have amorphous properties and interact transiently with a variety of other cellular proteins, including molecular chaperones, and they also bind stably with components of the ubiquitin-proteasome system and correlate with cell death (34)(35)(36)(37)(38). Furthermore, all three inclusion subtypes, TDP-43, FUS, and SOD1, are formed by mechanisms distinct from the highly structured amyloid aggregates of huntingtin (33).…”

mentioning

confidence: 99%

Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS

Ciryam

Lambert-Smith

Bean

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a heterogeneous degenerative motor neuron disease linked to numerous genetic mutations in apparently unrelated proteins. These proteins, including SOD1, TDP-43, and FUS, are highly aggregation-prone and form a variety of intracellular inclusion bodies that are characteristic of different neuropathological subtypes of the disease. Contained within these inclusions are a variety of proteins that do not share obvious characteristics other than coaggregation. However, recent evidence from other neurodegenerative disorders suggests that diseaseaffected biochemical pathways can be characterized by the presence of proteins that are supersaturated, with cellular concentrations significantly greater than their solubilities. Here, we show that the proteins that form inclusions of mutant SOD1, TDP-43, and FUS are not merely a subset of the native interaction partners of these three proteins, which are themselves supersaturated. To explain the presence of coaggregating proteins in inclusions in the brain and spinal cord, we observe that they have an average supersaturation even greater than the average supersaturation of the native interaction partners in motor neurons, but not when scores are generated from an average of other human tissues. These results suggest that inclusion bodies in various forms of ALS result from a set of proteins that are metastable in motor neurons, and thus prone to aggregation upon a disease-related progressive collapse of protein homeostasis in this specific setting.protein aggregation | protein misfolding | protein homeostasis | supersaturation | motor neuron disease

show abstract

The small heat shock proteins αB-crystallin and Hsp27 suppress SOD1 aggregation in vitro

Cited by 79 publications

References 54 publications

Negative Regulation of NADPH Oxidase 4 by Hydrogen Peroxide-inducible Clone 5 (Hic-5) Protein

Negative Regulation of NADPH Oxidase 4 by Hydrogen Peroxide-inducible Clone 5 (Hic-5) Protein

Small heat-shock proteins: important players in regulating cellular proteostasis

Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS

Contact Info

Product

Resources

About