Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin.

Ingolia, Thomas D.; Craig, Elizabeth A.

doi:10.1073/pnas.79.7.2360

Cited by 750 publications

(363 citation statements)

References 28 publications

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“…elevated temperature [38]. Horwitz's observation was an experimental verification of Ingolia and Craig's earlier classification of c as a member of the sHsp molecular chaperone family [39]. In the lens, the chaperone ability of c is of paramount importance in that it prevents the aggregation and precipitation of the crystallin proteins and hence delays the onset of age-related cataract.…”

Section:  -Crystallin In the Lensmentioning

confidence: 75%

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

Treweek

Meehan

Ecroyd

et al. 2014

Cell. Mol. Life Sci.

180

177

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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.

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Section:  -Crystallin In the Lensmentioning

confidence: 75%

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

Treweek

Meehan

Ecroyd

et al. 2014

Cell. Mol. Life Sci.

180

177

View full text Add to dashboard Cite

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“…Sequence homologies to proteins with known function could reveal the HSP's role. In fact, one HSP sequence, a stretch of 75 amino acids which are conserved among four small Drosophila HSPs, is 50% homologous to the B chain of mammalian lens alpha crystallin (32), suggesting that these HSPs may serve some kind of structural role. The complete amino acid sequences for HSP70 from E. coli, S. cerevisiae, Drosophila, and humans reveal very highly (>80%) conserved sequences throughout the polypeptide (2,31,42).…”

Section: Approaches To the Problemmentioning

confidence: 99%

Heat shock proteins: the search for functions.

Schlesinger¹

1986

The Journal of Cell Biology

369

109

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“…52 Both a-crystallins and Hsp27 are closely related family members. [19][20]61 aA/B-crystallins are initially known as major lens structural proteins that play an essential role in maintaining the transparency of the ocular lens. 62 Later, a-crystallins are found to act as molecular chaperones [63][64][65][66][67] and also display autokinase activity.…”

Section: Introductionmentioning

confidence: 99%

Human αA- and αB-crystallins bind to Bax and Bcl-XS to sequester their translocation during staurosporine-induced apoptosis

et al. 2004

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aA-and aB-crystallins are distinct antiapoptotic regulators. Regarding the antiapoptotic mechanisms, we have recently demonstrated that aB-crystallin interacts with the procaspase-3 and partially processed procaspase-3 to repress caspase-3 activation. Here, we demonstrate that human aA-and aBcrystallins prevent staurosporine-induced apoptosis through interactions with members of the Bcl-2 family. Using GST pulldown assays and coimmunoprecipitations, we demonstrated that a-crystallins bind to Bax and Bcl-X S both in vitro and in vivo. Human aA-and aB-crystallins display similar affinity to both proapoptotic regulators, and so are true with their antiapoptotic ability tested in human lens epithelial cells, human retina pigment epithelial cells (ARPE-19) and rat embryonic myocardium cells (H9c2) under treatment of staurosporine, etoposide or sorbitol. Two prominent mutants, R116C in aA-crystallin and R120G, in aB-crystallin display much weaker affinity to Bax and Bcl-X S . Through the interaction, a-crystallins prevent the translocation of Bax and Bcl-X S from cytosol into mitochondria during staurosporine-induced apoptosis. As a result, a-crystallins preserve the integrity of mitochondria, restrict release of cytochrome c, repress activation of caspase-3 and block degradation of PARP. Thus, our results demonstrate a novel antiapoptotic mechanism for a-crystallins. Keywords: aA-crystallin; R116C; aB-crystallin; R120G; Bax; Bcl-X S Abbreviations: a-crystallin, alpha-crystallin; GFP, green fluorescence protein; HaA, human aA-crystallin; HaB, human aB-crystallin; GFP-HaA, green fluorescence and human aAcrystallin fusion protein; GFP-HaB, green fluorescence and human aB-crystallin fusion protein; MEM, Eagle's minimal essential medium; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate-buffered saline; PMSF, phenylmethylsufonyl fluoride; HLE, human lens epithelial cells; SDS, sodium dodecylsulfate; TBS, tris-buffered saline; TBS-T, tris-buffered saline with tween-20.

show abstract

Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin.

Cited by 750 publications

References 28 publications

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

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

Heat shock proteins: the search for functions.

Human αA- and αB-crystallins bind to Bax and Bcl-XS to sequester their translocation during staurosporine-induced apoptosis

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