Selenoprotein K Binds Multiprotein Complexes and Is Involved in the Regulation of Endoplasmic Reticulum Homeostasis

Shchedrina, Valentina A.; Everley, Robert A.; Zhang, Yan; Gygi, Steven P.; Hatfield, Dolph L.; Gladyshev, Vadim N.

doi:10.1074/jbc.m111.310920

Cited by 117 publications

(133 citation statements)

References 53 publications

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“…95 Derlin-1 and -2 are strong candidates to play the role of channel proteins responsible for the retrotranslocation of unfolded proteins from the ER to the cytosol, the early stage of ERAD. Recent studies have shown that both SelS and SelK are associated with Derlins and p97 ATPase, with which may form an ER-membrane associate complex.…”

Section: Selenoproteins S and Kmentioning

confidence: 99%

“…Recent studies have shown that both SelS and SelK are associated with Derlins and p97 ATPase, with which may form an ER-membrane associate complex. 95 SelS may mediate the interaction of cytosolic p97 and Derlin-1, 96 but such an assumption still needs to be confirmed. Additional partners of SelS in the complex may be required to exploit its function, and SelK seems to be a potential candidate.…”

Section: Selenoproteins S and Kmentioning

confidence: 99%

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Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

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Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

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Section: Selenoproteins S and Kmentioning

confidence: 99%

Section: Selenoproteins S and Kmentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

View full text Add to dashboard Cite

show abstract

“…3, A and B) (25). Both SelS and SelK are involved in the ERAD complex and associate with p97(VCP) and derlins (12,24,25). It is well known that SelS functions in cell survival by regulating ER stress (17,26).…”

mentioning

confidence: 99%

“…SelS, which is also known as VCP-interacting membrane protein, is a selenoprotein that contains a single selenocysteine (Sec, U) at position 188, which is the penultimate C-terminal residue (21)(22)(23). SelS is an important component of the ERAD complex and is localized to the ER membrane together with SelK (24). Similarly to SelS, SelK is a selenoprotein that contains a single Sec at position 92 as the penultimate C-terminal residue, but it has no VIM or coiled-coil domain (Fig.…”

mentioning

confidence: 99%

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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“…Among them, selenoprotein K (SEPK) has a role in the immune system (28) , whereas selenoprotein N affects Ca homoeostasis (29) and selenoprotein P (SEPP) has an antioxidant protection function (30) . Moreover, transfer RNA (tRNA) selenocysteine 1-associated protein 1b (SECP43) has a major role in SEP synthesis by inserting selenocysteine into SEP (31) .…”

mentioning

confidence: 99%

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salarL.) fed diets with graded levels of plant ingredients

et al. 2016

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Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1-associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient.

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Selenoprotein K Binds Multiprotein Complexes and Is Involved in the Regulation of Endoplasmic Reticulum Homeostasis

Cited by 117 publications

References 53 publications

Selenium biochemistry and its role for human health

Selenium biochemistry and its role for human health

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

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salarL.) fed diets with graded levels of plant ingredients

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