Bag1 Functions In Vivo as a Negative Regulator of Hsp70 Chaperone Activity

Nollen, Ellen A. A.; Brunsting, Jeanette F.; Song, Jaewhan; Kampinga, Harm H.; Morimoto, Richard I.

doi:10.1128/mcb.20.3.1083-1088.2000

Cited by 131 publications

(128 citation statements)

References 35 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…Expression profiles of Hsp70 and Hsp60 were not altered after time- increased in Bag-1L+cells compared to wt HeLa cells. It was suggested that Bag1 formed a stoichiometric complex with Hsp70 and inhibited completely Hsp70-dependent in vitro protein refolding of an unfolded polypeptide (Nollen et al, 2000). Contrary to this finding, neuroprotective role of forced Bag-1 expression was found associated with the activation of Hsp70 to proceed cell survival (Liman et al, 2005).…”

Section: Discussioncontrasting

confidence: 52%

Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

Ozfiliz

Arısan²,

Gürkan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Cisplatin, a DNA damaging agent, induces apoptosis through increasing DNA fragmentation. However, identification of intrinsic resistance molecules against Cisplatin is vital to estimate the success of therapy. Bag-1 (Bcl-2-associated anthanogene) is one anti-apoptotic protein involved in drug resistance impacting on therapeutic efficiency. Elevated levels of this protein are related with increase cell proliferation rates, motility and also cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatininduced apoptosis in HeLa cervix cancer cells. Cisplatin decreased cell viability in time-and dose-dependent manner in wt and Bag-1L+HeLa cells. Although, 10μM Cisplatin treatment induced cell death within 24h by activating caspases in wt cells, Bag-1L stable transfection protected cells against Cisplatin treatment. To assess the potential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners of Bag-1. We found that forced Bag-1L expression prevented Cisplatin-induced apoptosis through acting on Mcl-1 expression, which was reduced after Cisplatin treatment in wt HeLa cells. This mechanism was also supported by the regulation of heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.

show abstract

Section: Discussioncontrasting

confidence: 52%

Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

Ozfiliz

Arısan²,

Gürkan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…In the mouse, two isoforms of Bag1 have been described, with the shorter one studied here representing the more abundant gene product by far. 22 The intracellular location of this Bag1 protein isoform may vary depending on cell background, environment and stage of differentiation, 22,32 In CSM14.1 cells, we detected Bag1 transgene expression predominantly in the nucleus of undifferentiated CSM14.1 cells. In contrast, p29 Bag1 is reportedly found predominantly in the cytosol of epithelial and hematopoietic cells.…”

Section: Discussionmentioning

confidence: 91%

Bag1 is a regulator and marker of neuronal differentiation

et al. 2002

View full text Add to dashboard Cite

Bag 1 acts as a co-chaperone for Hsp70/Hsc70. We report here that stable over-expression of Bag1 in immortalized neuronal CSM14.1 cells prevents death following serum deprivation. Bag1 over-expression slowed the proliferative rate of CSM14.1 cells, resulted in increased levels of phospo-MAP kinases and accelerated neuronal differentiation. Immunocytochemistry revealed mostly nuclear localization of Bag1 protein in these cells. However, during differentiation in vitro, Bag1 protein shifted from predominantly nuclear to mostly cytosolic in CSM14.1 cells. To explore in vivo parallels of these findings, we investigated Bag1 expression in the developing mouse nervous system using immunohistochemical methods. Early in brain development, Bag1 was found in nuclei of neuronal precursor cells, whereas cytosolic Bag1 staining was observed mainly after completion of neuronal precursor migration and differentiation. Taken together, these findings raise the possibility that the Bag1 protein is expressed early in neurogenesis in vivo and is capable of modulating neuronal cell survival and differentiation at least in part from a nuclear location.

show abstract

“…Another example how chaperoning determines CR signaling is that the ratio between hsp70 and a protein that binds hsp70 as a co-chaperone, termed BAG-1 (Bcl-2-associated gene product-1) modulates the glucocorticoid-binding activity of the GR hsp90 heterocomplex, as increasing BAG-1 inhibits GR folding and thus decreases corticosteroid signaling (Kanelakis et al 1999;Nollen et al 2000). From these findings, it can be concluded that changes in the chaperone assembly can have a manifold of effects on activation and repression of GRE-regulated genes.…”

Section: Cytosolic Activitiesmentioning

confidence: 99%

The Corticosteroid Receptor Hypothesis of Depression

Holsboer

2000

Neuropsychopharmacology

1,958

1,228

View full text Add to dashboard Cite

Clinical EvidenceUntil now, the serendipitous discovery of antidepressants in the 1950s has profoundly inspired hypotheses of the pathogenesis of depression. The well-known pharmacological effects of antidepressants on presynaptic uptake transporters and degradating enzymes (i.e., MAO) of serotonin and norepinephrine has focused research on causality and treatment of depression on the metabolism of functional biogenic amines and the capacity of their respective receptors to alter intracellular signaling pathways that ultimately induce changes in gene activity. Elevated circulating levels of stress hormones among depressives were recognized even before antidepressants were discovered, but these changes were seen as epiphenomena, reflecting the stressful experience of depression, although M. Bleuler (1919) already demonstrated that hormones have diverse psychotropic effects and suggested hormone treatments as potential antidepressants. A vast amount of evidence has accumulated, that reject the view that altered stress hormone secretions in depression are epiphenomenal. During the past decade, several research groups formulated a hypothesis relating aberrant stress hormone dysregulation to causality of depression and submitted that antidepressants may act through normalisation of these HPA changes (

show abstract

Bag1 Functions In Vivo as a Negative Regulator of Hsp70 Chaperone Activity

Cited by 131 publications

References 35 publications

Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

Bag1 is a regulator and marker of neuronal differentiation

The Corticosteroid Receptor Hypothesis of Depression

Contact Info

Product

Resources

About