Selenoprotein K and protein palmitoylation.

Abstract:

SIGNIFICANCE:Selenoprotein K (SelK) is an endoplasmic reticulum (ER) membrane protein, and its expression is sensitive to dietary selenium levels. A recently described role for SelK as a cofactor in catalyzing protein palmitoylation reactions provides an important link between low dietary selenium intake and suboptimal cellular functions that depend on this selenoprotein for palmitoylation. RECENT ADVANCES:A recent breakthrough provided insight into the contribution of SelK to calcium (Ca(2+)) flux in immune cells. In particular, SelK is required for palmitoylation of the Ca(2+) channel protein, inositol-1,4,5-triphosphate receptor (IP3R) in the ER membrane. Without this post-translational modification, expression and function of the IP3R is impaired. SelK is required for palmitoylation of another transmembrane protein, CD36, and very likely other proteins. SelK serves as a cofactor during protein palmitoylation by binding to the protein acyltransferase, DHHC6, thereby facilitating addition of the palmitate via a thioester bond to the sulfhydryl group of cysteine residues of target proteins. CRITICAL ISSUES:The association of DHHC6 and SelK is clearly important for immune cell functions and possibly other cell types. The step in the DHHC6 catalyzed S-acylation reaction on which SelK acts remains unclear and possible mechanisms of how the kinetics of the reaction are impacted by SelK binding to DHHC6 are presented here. FUTURE DIRECTIONS:Uncovering the specific role of SelK in promoting DHHC6 catalyzed protein palmitoylation may open a new line of inquiry into other selenoproteins playing similar roles as cofactors for different enzymatic processes.

journal_name

Antioxid Redox Signal

authors

Fredericks GJ,Hoffmann PR

doi

10.1089/ars.2015.6375

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

854-62

issue

10

eissn

1523-0864

issn

1557-7716

journal_volume

23

pub_type

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