Activation of OASIS family, ER stress transducers, is dependent on its stabilization

Kondo, Shinichi; Si, Hino; Saito, Atsushi; Kanemoto, Soshi; Kawasaki, Noritaka; Asada, Rie; Izumi, Soutarou; Iwamoto, Hideo; M, Oki; Miyagi, Hidetaka; Kaneko, Masayuki; Nomura, Yasuyuki; Urano, Fumihiko; Imaizumi, Kazunori

doi:10.1038/cdd.2012.77

Cited by 44 publications

(46 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S5b and S5c). Western blot analysis also revealed that in the presence of BFA CREB3 levels increase beyond the weakly detectable levels observed under basal conditions presumably due to inherent instability 36,37 (Figs. 6b and 6c).…”

Section: Resultsmentioning

confidence: 93%

A CREB3–ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens

et al. 2013

View full text Add to dashboard Cite

SUMMARY Treatment of cells with Brefeldin A (BFA) blocks secretory vesicle transport and causes a collapse of the Golgi apparatus. To gain more insight into the cellular mechanisms mediating BFA toxicity, we conducted a genome-wide haploid genetic screen that led to the identification of the small G protein ADP-ribosylation factor 4 (ARF4). ARF4 depletion preserves viability, Golgi integrity and cargo trafficking in the presence of BFA, and these effects depend on the guanine nucleotide exchange factor GBF1 and other ARF isoforms including ARF1 and ARF5. ARF4 knockdown cells show increased resistance to several human pathogens including Chlamydia trachomatis and Shigella flexneri. Furthermore, ARF4 expression is induced when cells are exposed to several Golgi-disturbing agents and requires the CREB3/Luman transcription factor whose downregulation mimics ARF4 loss. Thus, we have uncovered a CREB3–ARF4 signaling cascade that may be part of a Golgi stress response set in motion by stimuli compromising Golgi capacity.

show abstract

Section: Resultsmentioning

confidence: 93%

A CREB3–ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens

et al. 2013

View full text Add to dashboard Cite

show abstract

“…[12][13][14] Controversial evidence was found in the regulation of the osteogenic differentiation of MSCs by 1 UPR activation. [15][16][17][18][19][20] However, how ER stress results in the abnormal differentiation of PDLSCs remains largely unknown.…”

mentioning

confidence: 99%

Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation

Xue

et al. 2016

Cell Death Differ

View full text Add to dashboard Cite

The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis. Cell Death and Differentiation (2016) 23, 1862-1872 doi:10.1038/cdd.2016; published online 22 July 2016The endoplasmic reticulum (ER) primarily functions in protein biosynthesis and folding, lipid trafficking, metabolism and intracellular calcium storage. Elevated physiological demand for protein folding can cause the accumulation of misfolded or unfolded proteins in the ER lumen, a state called ER stress.

show abstract

“…19 However, the S2P cleavage site of BBF2H7 has not been identified ( Figure 1A). 32 The double bands of the N-termini were derived from fragments cleaved by S1P (higher) and S2P (lower), respectively ( Figure 1B). The 85 and 80 kDa full-length BBF2H7 [BBF2H7(F)] [glycosylated (higher) and unglycosylated forms (lower)] 19 were gradually increased in HEK293T cells transfected with an expression vector for BBF2H7 by treatment with thapsigargin (Tg, which is an ER stressor) ( Figure 1B).…”

Section: Intramembrane Proteolysis Of Bbf2h7mentioning

confidence: 99%

“…BBF2H7 is a notably unstable protein that is easily degraded via the ubiquitinproteasome pathway under normal conditions. 32 ER stress conditions enhance its stability because of avoidance from the degradation system. The stabilized BBF2H7 is translocated to the Golgi apparatus, followed by cleavage by S1P and S2P.…”

Section: Intramembrane Proteolysis Of Bbf2h7mentioning

confidence: 99%

Production of BBF2H7‐derived small peptide fragments via endoplasmic reticulum stress‐dependent regulated intramembrane proteolysis

et al. 2019

View full text Add to dashboard Cite

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. AbstractIntramembrane cleavage of transmembrane proteins is a fundamental cellular process to produce important signals that elicit biological responses. These proteolytic events are known as regulated intramembrane proteolysis (RIP). ATF6 and BBF2H7 are transmembrane basic leucine zipper transcription factors and are subjected to RIP by site-1 protease (S1P) and site-2 protease (S2P) sequentially in response to endoplasmic reticulum (ER) stress. However, the detailed mechanisms responsible for RIP of the transcription factors, including the precise cutting sites, are still unknown. In this study, we demonstrated that S1P cleaves BBF2H7 just before the RXXL S1P recognition motif. Conversely, S2P cut at least three different sites in the membrane (next to Leu380, Met381, and Leu385), indicating that S2P cleaves the substrates at variable sites or via a multistep process. Interestingly, we found BBF2H7-derived small peptide (BSP) fragments located between the S1P and S2P cleavage sites in cells exposed to ER stress. Major type of BSP fragments was composed of 45 amino acid including partial transmembrane and luminal regions and easily aggregates like amyloid β (Aβ) protein. These results advance the understanding of poorly characterized ER stress-dependent RIP. Furthermore, the aggregable peptides produced by ER stress could link to the pathophysiology of neurodegenerative disorders. |MATSUHISA eT Al.

show abstract

Activation of OASIS family, ER stress transducers, is dependent on its stabilization

Cited by 44 publications

References 38 publications

A CREB3–ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens

A CREB3–ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens

Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation

Production of BBF2H7‐derived small peptide fragments via endoplasmic reticulum stress‐dependent regulated intramembrane proteolysis

Contact Info

Product

Resources

About