BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism

Rodríguez, Andrea; López-Crisosto, Camila; Peña‐Oyarzún, Daniel; Salas, Daniela; Parra, Valentina; Quiroga, Clara; Morawe, Tobias; Chiong, Mario; Behl, Christian; Lavandero, Sergio

doi:10.1080/15548627.2015.1124225

Cited by 31 publications

(28 citation statements)

References 32 publications

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“…A recent report in the literature has shown that BAG3 actually regulates the basal amount of total cellular LC3B by controlling its mRNA translation. This was specific for LC3, since no other ATG proteins were found to be affected in that study (Rodríguez et al, 2016). We have observed, however, decreased Atg5 protein levels in siBAG3-transfected TM cells.…”

Section: Autophagy and Mechanical Stretch: Dual Role In Repair Andmentioning

confidence: 67%

Autophagy and mechanotransduction in outflow pathway cells

Hirt

Liton

2017

Experimental Eye Research

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Because of elevations in IOP and other forces, cells in the trabecular meshwork (TM) are constantly subjected to mechanical strain. In order to preserve cellular function and regain homeostasis, cells must sense and adapt to these morphological changes. We and others have already shown that mechanical stress can trigger a broad range of responses in TM cells; however, very little is known about the strategies that TM cells use to respond to this stress, so they can adapt and survive. Autophagy, a lysosomal degradation pathway, has emerged as an important cellular homeostatic mechanism promoting cell survival and adaptation to a number of cytotoxic stresses. Our laboratory has reported the activation of autophagy in TM cells in response to static biaxial strain and high pressure. Moreover, our newest data also suggest the activation of chaperon-assisted selective autophagy, a recently identified tension-induced autophagy essential for mechanotransduction, in TM cells under cyclic mechanical stress. In this review manuscript we will discuss autophagy as part of an integrated response triggered in TM cells in response to strain, exerting a dual role in repair and mechanotransduction, and the potential effects of dysregulated in outflow pathway pathophysiology.

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Section: Autophagy and Mechanical Stretch: Dual Role In Repair Andmentioning

confidence: 67%

Autophagy and mechanotransduction in outflow pathway cells

Hirt

Liton

2017

Experimental Eye Research

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“…Evidently, BAG3 facilitates the clearance of damaged Tom20 and its down regulation increases the level of Parkin translocation to the mitochondria after CCCP treatment. It was previously reported that BAG3 knock-down increased the amount of mitochondria in HeLa cells (Rodríguez et al, 2016). The accumulation of dysfunctional mitochondria within cells has been implicated in the development of neurodegenerative disorders such as Parkinson's disease.…”

Section: Discussionmentioning

confidence: 97%

“…Recent studies have demonstrated enhanced expression of BAG3 and increased levels of its chaperonic activity along with heat shock proteins during cellular stress and aging, suggesting a crucial role for BAG3 in determining the cellular stress response (Behl et al, 2011). BAG3 is known to play an important role in intracellular protein homeostasis by participating either in protein folding and/or clearance of damaged proteins (Rodriguez et al, 2016). To this end, BAG3 functions along with other proteins such as SQSTM1/P62 (referred to as P62 from here on), HSP70, and LC3 in a process called macroautophagy in which misfolded or damaged proteins and organelles are sequestered within autophagosomes and targeted to lysosomes for degradation (Behl et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Role of BAG3 in Mitochondrial Quality Control in Cardiomyocytes

Tahrir

Knezevic

Gupta

et al. 2016

Journal Cellular Physiology

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Mitochondrial abnormalities impact the development of myofibrillar myopathies. Therefore, understanding the mechanisms underlying the removal of dysfunctional mitochondria from cells is of great importance toward understanding the molecular events involved in the genesis of cardiomyopathy. Earlier studies have ascribed a role for BAG3 in the development of cardiomyopathy in experimental animals leading to the identification of BAG3 mutations in patients with heart failure which may play a part in the onset of disease development and progression. BAG3 is co-chaperone of heat shock protein 70 (HSP70), which has been shown to modulate apoptosis and autophagy, in several cell models. In this study, we explore the potential role of BAG3 in mitochondrial quality control. We demonstrate that siRNA mediated suppression of BAG3 production in neonatal rat ventricular cardiomyocytes (NRVCs) significantly elevates the level of Parkin, a key component of mitophagy. We found that both BAG3 and Parkin are recruited to depolarized mitochondria and promote mitophagy. Suppression of BAG3 in NRVCs significantly reduces autophagy flux and eliminates expression of Tom20, an essential import receptor for mitochondria proteins, after induction of mitophagy. These observations suggest that BAG3 is critical for the maintenance of mitochondrial homeostasis under stress conditions, and disruptions in BAG3 expression impact cardiomyocyte function.

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“…Previous studies, as well as increasing evidence, support this postulation as BIS has been shown to regulate several proteins, including microtubule-associated protein 1 light chain 3β (MAP1LC3B) [32], STAT3 [16], and myosin heavy chain [33]. …”

Section: Discussionmentioning

confidence: 99%

Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties

Yun

Lee

2017

IJMS

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Heat shock factor 1 (HSF1), a transcription factor activated by various stressors, regulates proliferation and apoptosis by inducing expression of target genes, such as heat shock proteins and Bcl-2 (B-cell lymphoma 2) interacting cell death suppressor (BIS). HSF1 also directly interacts with BIS, although it is still unclear whether this interaction is critical in the regulation of glioblastoma stem cells (GSCs). In this study, we examined whether small interfering RNA-mediated BIS knockdown decreased protein levels of HSF1 and subsequent nuclear localization under GSC-like sphere (SP)-forming conditions. Consistent with BIS depletion, HSF1 knockdown also reduced sex determining region Y (SRY)-box 2 (SOX2) expression, a marker of stemness, accompanying the decrease in SP-forming ability and matrix metalloprotease 2 (MMP2) activity. When HSF1 or BIS knockdown was combined with temozolomide (TMZ) treatment, a standard drug used in glioblastoma therapy, apoptosis increased, as measured by an increase in poly (ADP-ribose) polymerase (PARP) cleavage, whereas cancer stem-like properties, such as colony-forming activity and SOX2 protein expression, decreased. Taken together, our findings suggest that targeting BIS or HSF1 could be a viable therapeutic strategy for GSCs resistant to conventional TMZ treatment.

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BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism

Cited by 31 publications

References 32 publications

Autophagy and mechanotransduction in outflow pathway cells

Autophagy and mechanotransduction in outflow pathway cells

Evidence for the Role of BAG3 in Mitochondrial Quality Control in Cardiomyocytes

Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties

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