A Ubiquitin Ligase-Associated Chaperone Holdase Maintains Polypeptides in Soluble States for Proteasome Degradation

Wang, Qiuyan; Liu, Yanfen; Soetandyo, Nia; Baek, Kheewoong; Hegde, Ramanujan S.; Ye, Yihong

doi:10.1016/j.molcel.2011.05.010

Cited by 193 publications

(292 citation statements)

References 42 publications

Supporting

Mentioning

276

Contrasting

Order By: Relevance

“…While assisting in protein biosynthesis on the one hand, BAG6 also mediates degradation of mislocalized nascent chains (Hessa et al, 2011) and ERAD substrates (Claessen and Ploegh, 2011;Claessen et al, 2014;Payapilly and High, 2014;Wang et al, 2011). Moreover, Rodrigo-Brenni et al (2014) recently described RNF126 as an E3 ligase interacting with BAG6 and specifically ubiquitylating chaperone bound client proteins (Rodrigo-Brenni et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…BAG6 maintains retrotranslocated ER-associated protein degradation (ERAD) substrates in a soluble state and thereby allows proteasomal degradation of these substrates (Claessen and Ploegh, 2011;Wang et al, 2011). To study the presentation of an epitope derived from a retrotranslocated protein we chose the tyrosinase epitope Tyr369-377(D).…”

Section: Presentation Of Retrotranslocated Tyrosinase-derived Epitopementioning

confidence: 99%

“…BAG6 is conserved in higher eukaryotes, ubiquitously expressed, and encoded in the MHC class III locus (Banerji et al, 1990;Ozaki et al, 1999;Wang and Liew, 1994). Even though BAG6 is clas-sified as a chaperone, it has no apparent folding activity (Wang et al, 2011). Together with its binding partners TRC35 and UBL4A it associates with long hydrophobic patches in client proteins and prevents aggregation (Leznicki et al, 2013;Mariappan et al, 2010;Minami et al, 2010;Wang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Even though BAG6 is clas-sified as a chaperone, it has no apparent folding activity (Wang et al, 2011). Together with its binding partners TRC35 and UBL4A it associates with long hydrophobic patches in client proteins and prevents aggregation (Leznicki et al, 2013;Mariappan et al, 2010;Minami et al, 2010;Wang et al, 2011). Therefore, BAG6 has also been described as a "holdase" which keeps its substrate in a soluble state (Wang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Together with its binding partners TRC35 and UBL4A it associates with long hydrophobic patches in client proteins and prevents aggregation (Leznicki et al, 2013;Mariappan et al, 2010;Minami et al, 2010;Wang et al, 2011). Therefore, BAG6 has also been described as a "holdase" which keeps its substrate in a soluble state (Wang et al, 2011). Because of its binding properties, BAG6 is especially involved in the biogenesis and degradation of polypeptides carrying hydrophobic domains (Kawahara et al, 2013;Lee and Ye, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Bitzer

Basler

Groettrup

2016

Molecular Immunology

View full text Add to dashboard Cite

a b s t r a c tAntigen processing for direct presentation on MHC class I molecules is a multistep process requiring the concerted activity of several cellular complexes. The essential steps at the beginning of this pathway, namely protein synthesis at the ribosome and degradation via the proteasome, have been known for years. Nevertheless, there is a considerable lack of factors identified to function between protein synthesis and degradation during antigen processing. Here, we analyzed the impact of the chaperone BAG6 on MHC class I cell surface expression and presentation of virus-derived peptides. Although an essential role of BAG6 in antigen processing has been proposed previously, we found BAG6 to be dispensable in this pathway. Still, interaction of BAG6 and the model antigen tyrosinase was enhanced during proteasome inhibition pointing towards a role of BAG6 in antigen degradation. Redundant chaperone pathways potentially mask the contribution of BAG6 to antigen processing and presentation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Presentation Of Retrotranslocated Tyrosinase-derived Epitopementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Bitzer

Basler

Groettrup

2016

Molecular Immunology

View full text Add to dashboard Cite

show abstract

Negative feedback and modern anti‐cancer strategies targeting the ER stress response

2020

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress is a cell state in which misfolded or unfolded proteins are aberrantly accumulated in the ER. ER stress induces an evolutionarily conserved adaptive response, named the ER stress response, that deploys a self-regulated machinery to maintain cellular proteostasis. However, compared to its well-established canonical activation mechanism, the negative feedback mechanisms regulating the ER stress response remain unclear and no accepted methods or markers have been established. Several studies have documented that both endogenous and exogenous insults can induce ER stress in cancer. Based on this evidence, small molecule inhibitors targeting ER stress response have been designed to kill cancer cells, with some of them showing excellent curative effects. Here, we review recent advances in our understanding of negative feedback of the ER stress response and compare the markers used to date. We also summarize therapeutic inhibitors targeting ER stress response and highlight the promises and challenges ahead.

show abstract

BAG6 deficiency induces mis‐distribution of mitochondrial clusters under depolarization

2019

View full text Add to dashboard Cite

Accumulation of damaged mitochondria is implicated in a number of neurodegenerative disorders, including Parkinson's disease. Therefore, the machinery for mitochondrial quality control is important for the prevention of such diseases. It has been reported that Parkin‐ and p62/sequestosome 1 (SQSTM1)‐mediated clustering and subsequent elimination of damaged mitochondria (termed mitophagy) are critical for maintaining the quality of mitochondria under stress induced by uncoupling agents such as carbonyl cyanide m ‐chlorophenyl hydrazone. However, the molecular mechanisms underlying mitochondrial translocation to the perinuclear region during mitophagy have not been adequately addressed to date. In this study, we found that BCL2‐associated athanogene 6 (BAG6; also known as BAT3 or Scythe) is required for this process. Indeed, RNA interference‐mediated depletion of endogenous BAG6 prevented Parkin‐dependent relocalization of mitochondrial clusters to the perinuclear cytoplasmic region, whereas BAG6 knockdown did not affect the translocation of Parkin and p62/SQSTM1 to the depolarized mitochondria and subsequent aggregation. These results suggest that BAG6 is essential for cytoplasmic redistribution, but not for clustering, of damaged mitochondria.

show abstract

A Ubiquitin Ligase-Associated Chaperone Holdase Maintains Polypeptides in Soluble States for Proteasome Degradation

Cited by 193 publications

References 42 publications

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Negative feedback and modern anti‐cancer strategies targeting the ER stress response

BAG6 deficiency induces mis‐distribution of mitochondrial clusters under depolarization

Contact Info

Product

Resources

About