HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis

Watanabe, Yoshihisa; Tsujimura, Akira; Taguchi, Katsutoshi; Tanaka, Masaki

doi:10.1080/15548627.2016.1248018

Cited by 64 publications

(48 citation statements)

References 52 publications

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“…Such a delay in ubiquitinated microaggregate formation was replicated by silencing of the autophagic adaptor p62, a known partner of BAG3 implicated in the sequestration of ubiquitinated proteins (Fig. 3D, E; sip62) (26,37,58).…”

Section: Hspb8 Promotes Early Formation Of Ubiquitinated Microaggregatesmentioning

confidence: 90%

“…5A, 1.5-, 2.5-fold increase). These 2 phospho-sites are thought to control ubiquitinated inclusion formation (37,62,65). Silencing of either HSPB8 or BAG3 impaired stress-induced p62 phosphorylation, leading to a significant reduction of S349phosphorylated p62 levels by 4 h after proteasome inhibition (;75% inhibition, pS349).…”

Section: Hspb8 and Bag3 Regulate The Molecular Assembly Of P62 And Kementioning

confidence: 99%

“…The heat shock factor (HSF)-1, which controls the expression of molecular chaperones, would regulate p62 phosphorylation and inclusion formation, upstream of kinase activities. (37). Whether BAG3 and its chaperone partners play a role has not been addressed.…”

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confidence: 99%

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HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency

et al. 2018

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BCL2-associated athanogene (BAG)-3 is viewed as a platform that would physically and functionally link distinct classes of molecular chaperones of the heat shock protein (HSP) family for the stabilization and clearance of damaged proteins. In this study, we show that HSPB8, a member of the small heat shock protein subfamily, cooperates with BAG3 to coordinate the sequestration of harmful proteins and the cellular adaptive response upon proteasome inhibition. Silencing of HSPB8, like depletion of BAG3, inhibited targeting of ubiquitinated proteins to the juxtanuclear aggresome, a mammalian system of spatial quality control. However, aggresome targeting was restored in BAG3-depleted cells by a mutant BAG3 defective in HSPB8 binding, uncoupling HSPB8 function from its binding to BAG3. Depletion of HSPB8 impaired formation of ubiquitinated microaggregates in an early phase and interfered with accurate modifications of the stress sensor p62/sequestosome (SQSTM)-1. This impairment correlated with decreased coupling of BAG3 to p62/SQSTM1 in response to stress, hindering Kelch-like ECH-associated protein (KEAP)-1 sequestration and stabilization of nuclear factor E2-related factor (Nrf)-2, an important arm of the antioxidant defense. Notably, the myopathy-associated mutation of BAG3 (P209L), which lies within the HSPB8-binding motif, deregulated the association between BAG3 and p62/SQSTM1 and the KEAP1-Nrf2 signaling axis. Together, our findings support a so-far-unrecognized role for the HSPB8-BAG3 connection in mounting of an efficient stress response, which may be involved in BAG3-related human diseases.-Guilbert, S. M., Lambert, H., Rodrigue, M.-A., Fuchs, M., Landry, J., Lavoie, J. N. HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency.

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Section: Hspb8 Promotes Early Formation Of Ubiquitinated Microaggregatesmentioning

confidence: 90%

Section: Hspb8 and Bag3 Regulate The Molecular Assembly Of P62 And Kementioning

confidence: 99%

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HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency

et al. 2018

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“…3B, step 3) (Ichimura et al, 2013;Komatsu et al, 2010). Multiple kinases, including casein kinase 1 (CSNK1A1), transforming growth factor beta-activated kinase 1 (TAK1, officially known as MAP3K7), mTORC1 and PKC-delta (PRKCD), promote this phosphorylation during selective autophagy (Hashimoto et al, 2016;Ichimura et al, 2013;Jiang et al, 2017;Watanabe et al, 2017).…”

Section: Box 1 Selective Autophagy Is Mediated By a Several Receptormentioning

confidence: 99%

p62/SQSTM1 – steering the cell through health and disease

Sánchez‐Martín

Komatsu

2018

Journal of Cell Science

232

179

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SQSTM1 (also known as p62) is a multifunctional stress-inducible scaffold protein involved in diverse cellular processes. Its functions are tightly regulated through an extensive pattern of post-translational modifications, and include the isolation of cargos degraded by autophagy, induction of the antioxidant response by the Keap1-Nrf2 system, as well as the regulation of endosomal trafficking, apoptosis and inflammation. Accordingly, malfunction of SQSTM1 is associated with a wide range of diseases, including bone and muscle disorders, neurodegenerative and metabolic diseases, and multiple forms of cancer. In this Review, we summarize current knowledge regarding regulation, post-translational modifications and functions of SQSTM1, as well as how they are dysregulated in various pathogenic contexts.

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“…Следует также отметить, что р62 может запускать и аутофагию протеасом [122]. Взаимодействие р62 с убиквитинированными белками значительно усиливается при фосфорилировании его сериновых остатков (S349, S403, S407), важную роль в ýтом играет фактор транскрипции HSF1 (heat shock transcription factor 1) [123]. [126].…”

Section: агрефагияunclassified

Autophagy as a protective mechanism in oxidative stress

et al. 2019

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1 Федеральный исследовательский центр фундаментальной и трансляционной медицины (ФИЦ ФТМ) Россия, 630117, г. Новосибирск, ул. Тимакова, 2 2 Белорусский государственный университет (БГУ) Республика Беларусь, 220030, г. Минск, пр. Независимости, 4 3 Новосибирский государственный педагогический университет (НГПУ) Россия, 630126, г. Новосибирск, ул. Вилюйская, 28 РЕЗЮМЕ Аутофагия является основным катаболическим процессом удаления из клеток поврежденных органелл, агрегированных белков и внутриклеточных патогенов. Развитие окислительного стресса сопровождается усилением аутофагии, которая оказывает защитное действие посредством поддержания качественного состава митохондрий (митофагия) и пероксисом (пексофагия) с последующей лизосомальной деградацией органелл с высокой продукцией активных форм кислорода. Посредством агрефагии также удаляются токсические продукты, образующиеся при окислительном и карбонильном стрессе. Кроме того, аутофагия может активировать систему антиоксидант-респонсивного ýлемента и повышать ýкспрессию генов антиоксидантных ферментов. Çащитная роль аутофагии может быть полезной при многих патологиях, сопровождающихся развитием окислительного стресса, и в то же время служить причиной химиорезистентности и снижать ýффективность противоопухолевой терапии. Ключевые слова: аутофагия, окислительный стресс, митохондрии, пероксисомы, система Keap1/ Nrf2/ARE. Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи. Источник финансирования. Исследование выполнено при поддержке РФФИ (грант 16-54-00050 Бел_а) и БФФИ (грант M16P-022). Для цитирования: Çенков Н.К., Чечушков А.В., Кожин П.М., Мартинович Г.Г., Кандалинцева Н.В., Меньщикова Е.Б. Аутофагия как механизм защиты при окислительном стрессе. Бюллетень сибирской медицины. 2019; 18 (2): 195-214. https://doi. ABSTRACTAutophagy is the main catabolic process required for the removal of damaged organelles, aggregated proteins and intracellular pathogens from cells. Oxidative stress is accompanied by an increase in autophagy, which has a protective effect by maintaining the qualitative composition of mitochondria (mitophagy) and peroxisomes (pexophagy) followed by lysosomal degradation of organelles with high production of reactive oxygen species. Aggrephagy also removes toxic products formed during oxidative and carbonyl stress. Furthermore, autophagy can activate the antioxidant response element system and increase the expression of antioxidant enzyme genes. The protective role of autophagy can be useful in many pathological processes accompanied by the development of oxidative stress while at the same time it may cause chemoresistance, reducing the effectiveness of anti-tumor therapy.

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HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis

Cited by 64 publications

References 52 publications

HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency

HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency

p62/SQSTM1 – steering the cell through health and disease

Autophagy as a protective mechanism in oxidative stress

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