The BAG proteins: a ubiquitous family of chaperone regulators

Kabbage, Mehdi; Dickman, Martin B.

doi:10.1007/s00018-008-7535-2

Cited by 259 publications

(290 citation statements)

References 89 publications

(101 reference statements)

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“…The BAG genes constitute a broadly conserved gene family and function as adapter proteins/cochaperones, forming complexes with signaling molecules and molecular chaperones including Hsp70 (Kabbage and Dickman, 2008;Williams et al, 2010). In mammals, BAG proteins are associated with several key cellular processes, including apoptosis, autophagy, proliferation, differentiation, and stress signaling (Takayama et al, 1999;Song et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Mutants Show Enhanced Susceptibility to B. cinerea Previously we described the identification and preliminary characterization of the Arabidopsis BAG gene family (Doukhanina et al, 2006;Kabbage and Dickman, 2008). T-DNA knockout lines were obtained for all seven members of the BAG gene family.…”

Section: Arabidopsis Bag6mentioning

confidence: 99%

“…The remaining three members contain a predicted calmodulin binding motif near the BAG domain, a feature unique to plant BAG proteins indicating possible divergent mechanisms associated with plantspecific functions. As noted for mammalian BAGs, plant BAGs also regulate several stress and developmental processes (Kabbage and Dickman, 2008;Williams et al, 2010). Thus structural approaches can be used for prediction of protein function independent of sequence similarity.…”

Section: Introductionmentioning

confidence: 99%

“…As an approach to address whether PCD-related genes have structural and, thus, possibly functional similarities to their mammalian counterparts, we used computational approaches searching for plant genes that structurally resembled apoptotic PCD genes, and as a result we uncovered the Bcl-2-associated athanogene (BAG) protein family in Arabidopsis thaliana (Doukhanina et al, 2006;Kabbage and Dickman, 2008). While plant and human BAG proteins have relatively low sequence identity that initially obscured detection by BLAST searches, these proteins were found to be remarkably similar in several key structural regions.…”

Section: Introductionmentioning

confidence: 99%

“…BAG proteins are distinguished by the presence of a common conserved C-terminal BAG domain that mediates their interaction with Hsp70/Hsc70 molecular chaperones (Brive et al, 2001;Takayama and Reed, 2001; Kabbage and Dickman, 2008). Six BAG family members have been identified in humans and regulate, both positively and negatively, the function of Hsp70/Hsc70 chaperones, forming complexes with a range of transcription factors and signaling proteins to modulate diverse physiological processes, including apoptosis, tumorigenesis, neuronal differentiation, stress responses, and cell cycle progression (Kabbage and Dickman, 2008). In contrast to mammals, far less is known about the structure and function of BAG proteins in plants.…”

Section: Introductionmentioning

confidence: 99%

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Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants

et al. 2016

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The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved group of cochaperones that modulate numerous cellular processes. Previously we found that Arabidopsis thaliana BAG6 is required for basal immunity against the fungal phytopathogen Botrytis cinerea. However, the mechanisms by which BAG6 controls immunity are obscure. Here, we address this important question by determining the molecular mechanisms responsible for BAG6-mediated basal resistance. We show that Arabidopsis BAG6 is cleaved in vivo in a caspase-1-like-dependent manner and via a combination of pulldowns, mass spectrometry, yeast two-hybrid assays, and chemical genomics, we demonstrate that BAG6 interacts with a C2 GRAM domain protein (BAGP1) and an aspartyl protease (APCB1), both of which are required for BAG6 processing. Furthermore, fluorescence and transmission electron microscopy established that BAG6 cleavage triggers autophagy in the host that coincides with disease resistance. Targeted inactivation of BAGP1 or APCB1 results in the blocking of BAG6 processing and loss of resistance. Mutation of the cleavage site blocks cleavage and inhibits autophagy in plants; disease resistance is also compromised. Taken together, these results identify a mechanism that couples an aspartyl protease with a molecular cochaperone to trigger autophagy and plant defense, providing a key link between fungal recognition and the induction of cell death and resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Arabidopsis Bag6mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants

et al. 2016

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Hsp70 – a master regulator in protein degradation

et al. 2017

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Edited by Wilhelm JustProteostasis, the controlled balance of protein synthesis, folding, assembly, trafficking and degradation, is a paramount necessity for cell homeostasis. Impaired proteostasis is a hallmark of ageing and of many human diseases. Molecular chaperones are essential for proteostasis in eukaryotic cells, and their function has traditionally been linked to protein folding, assembly and disaggregation. More recent findings suggest that chaperones also contribute to key steps in protein degradation. In particular, Hsp70 has an essential role in substrate degradation through the ubiquitin-proteasome system, as well as through different autophagy pathways. Accumulated knowledge suggests that the fate of an Hsp70 substrate is dictated by the combination of partners (cochaperones and other chaperones) that interact with Hsp70 in a given cell context.

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The roles of molecular chaperones in regulating cell metabolism

Binder

Pedley

2023

FEBS Letters

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Fluctuations in nutrient and biomass availability, often as a result of disease, impart metabolic challenges that must be overcome in order to sustain cell survival and promote proliferation. Cells adapt to these environmental changes and stresses by adjusting their metabolic networks through a series of regulatory mechanisms. Our understanding of these rewiring events has largely been focused on those genetic transformations that alter protein expression and the biochemical mechanisms that change protein behavior, such as post‐translational modifications and metabolite‐based allosteric modulators. Mounting evidence suggests that a class of proteome surveillance proteins called molecular chaperones also can influence metabolic processes. Here, we summarize several ways the Hsp90 and Hsp70 chaperone families act on human metabolic enzymes and their supramolecular assemblies to change enzymatic activities and metabolite flux. We further highlight how these chaperones can assist in the translocation and degradation of metabolic enzymes. Collectively, these studies provide a new view for how metabolic processes are regulated to meet cellular demand and inspire new avenues for therapeutic intervention.

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The BAG proteins: a ubiquitous family of chaperone regulators

Cited by 259 publications

References 89 publications

Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants

Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants

Hsp70 – a master regulator in protein degradation

The roles of molecular chaperones in regulating cell metabolism

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