SelK is a novel ER stress-regulated protein and protects HepG2 cells from ER stress agent-induced apoptosis

Du, Shaoqing; Zhou, Jun; Jia, Yi; Huang, Kaixun

doi:10.1016/j.abb.2010.08.001

Cited by 84 publications

(74 citation statements)

References 49 publications

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“…Cleavage by m-Calpain Is Responsible for the Two SelK Isoforms-SelK has been suggested to be transcriptionally upregulated during ER stress (20). However, we found that TLR ligands did not increase SelK mRNA levels nor did they induce ER stress (supplemental Figs.…”

Section: Isoforms Of Selk In Myeloid Cellscontrasting

confidence: 50%

Selenoprotein K Is a Novel Target of m-Calpain, and Cleavage Is Regulated by Toll-like Receptor-induced Calpastatin in Macrophages

Huang

Hoffmann

Norton

et al. 2011

Journal of Biological Chemistry

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Background: Selenoprotein K is important for calcium-dependent activation of immune cells. Results: Selenoprotein K is cleaved by m-calpain in resting macrophages, but Toll-like receptor activation induces calpastatin generating full-length, functional selenoprotein K. Conclusion: Proteolytic modulation of selenoprotein K is important for macrophage activation. Significance: New roles are defined for the calpain/calpastatin system and selenoprotein K during macrophage activation and inflammation.

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Section: Isoforms Of Selk In Myeloid Cellscontrasting

confidence: 50%

Selenoprotein K Is a Novel Target of m-Calpain, and Cleavage Is Regulated by Toll-like Receptor-induced Calpastatin in Macrophages

Huang

Hoffmann

Norton

et al. 2011

Journal of Biological Chemistry

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“…Furthermore, SelS is known to be associated with the maintenance and intracellular membrane-based transport of multiprotein complexes (39). SelK has been reported to regulate Ca 2ϩ flux during immune responses and to protect cells from ER stress-mediated apoptosis (27,50). However, the way in which SelS and SelK interact and the subsequent effect on the ER stress response is not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…To induce ER stress, N2a cells were seeded at a density of 1 ϫ 10 6 cells, and HEK293 cells were seeded at a density of 3 ϫ 10 5 cells in 60-mm dishes. 24 h after seeding, the cells were treated with 1 g/ml tunicamycin (Tm) and 100 nM thapsigargin or dimethyl sulfoxide (Sigma-Aldrich) (27,28) for 24 h.…”

Section: Methodsmentioning

confidence: 99%

“…The location of p97(VCP) is important for its subcellular function (10), and the protein is translocalized to the ER membrane via its interaction with SelS to participate in ERAD during ER stress (9,12). It has been reported that the expression of SelS and SelK is increased in various cell types that have been treated with various ER stress inducers, such as Tm and thapsigargin (24,27,36). In this study, increased expression levels were observed for both selenoproteins in N2a cells that had been treated with 1 g/ml Tm or 100 nM thapsigargin for 24 h, and the translocation of p97(VCP) to the ER membrane was increased (Fig.…”

Section: Er Stress Enhances the Expression Of Sels And Selk And The Tmentioning

confidence: 99%

“…It is well known that SelS functions in cell survival by regulating ER stress (17,26). Recent studies have suggested that SelK is also an ER stress-regulated protein and plays an important role in resisting ER stress-mediated apoptosis (27).…”

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confidence: 99%

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Selenoprotein S-dependent Selenoprotein K Binding to p97(VCP) Protein Is Essential for Endoplasmic Reticulum-associated Degradation

Lee

Park

Jang

et al. 2015

Journal of Biological Chemistry

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Cytosolic valosin-containing protein (p97(VCP)) is translocated to the ER membrane by binding to selenoprotein S (SelS), which is an ER membrane protein, during endoplasmic reticulum-associated degradation (ERAD). Selenoprotein K (SelK) is another known p97(VCP)-binding selenoprotein, and the expression of both SelS and SelK is increased under ER stress. To understand the regulatory mechanisms of SelS, SelK, and p97(VCP) during ERAD, the interaction of the selenoproteins with p97(VCP) was investigated using N2a cells and HEK293 cells. Both SelS and SelK co-precipitated with p97(VCP). However, the association between SelS and SelK did not occur in the absence of p97(VCP). SelS had the ability to recruit p97(VCP) to the ER membrane but SelK did not. The interaction betweenSelK and p97(VCP) did not occur in SelS knockdown cells, whereas SelS interacted with p97(VCP) in the presence or absence of SelK. These results suggest that p97(VCP) is first translocated to the ER membrane via its interaction with SelS, and then SelK associates with the complex on the ER membrane. Therefore, the interaction between SelK and p97(VCP) is SelSdependent, and the resulting ERAD complex (SelS-p97(VCP)-SelK) plays an important role in ERAD and ER stress.

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Selenoproteins in Cellular Redox Regulation and Signaling

Raman

Berry

2011

Oxidative Stress in Vertebrates and Invertebrates

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SelK is a novel ER stress-regulated protein and protects HepG2 cells from ER stress agent-induced apoptosis

Cited by 84 publications

References 49 publications

Selenoprotein K Is a Novel Target of m-Calpain, and Cleavage Is Regulated by Toll-like Receptor-induced Calpastatin in Macrophages

Selenoprotein K Is a Novel Target of m-Calpain, and Cleavage Is Regulated by Toll-like Receptor-induced Calpastatin in Macrophages

Selenoprotein S-dependent Selenoprotein K Binding to p97(VCP) Protein Is Essential for Endoplasmic Reticulum-associated Degradation

Selenoproteins in Cellular Redox Regulation and Signaling

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