@article {3095173,
	title = {An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machinery.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {103},
	year = {2006},
	month = {2006 Jul 25},
	pages = {11178-83},
	abstract = {Serum- and glucocorticoid-induced kinase 1 (Sgk1) regulates many ion channels and transporters in epithelial cells and promotes cell survival under stress conditions. In this study we demonstrate that Sgk1 is a short-lived protein regulated by the endoplasmic reticulum (ER)-associated degradation system and subcellular localization to the ER. We identified a hydrophobic motif (residues 18-30) as the signal for ER localization and rapid degradation by the ubiquitin (Ub)/proteasome pathway in both yeast and mammalian cells. Deletion or reduction of hydrophobicity of the motif redistributes Sgk1 to the cytosol and nucleus and markedly increases its half-life. We determined that the Ub-conjugating UBC6 and UBC7 and the Ub ligase HRD1 are the ER-associated Ub enzymes that mediate degradation of Sgk1; thus, Sgk1 has been identified as a cytosolic substrate for mammalian HRD1. Compartmentalization of Sgk1 controls the functional and spatial specificities of Sgk1-mediated signaling pathways, whereas rapid protein turnover provides a means to rapidly adjust Sgk1 abundance in response to different hormonal and external stimuli that increase Sgk1 gene transcription.},
	keywords = {Animals, Cell Nucleus, CHO Cells, Cricetinae, Cytosol, Endoplasmic Reticulum, Fungal Proteins, Humans, Immediate-Early Proteins, Mice, Models, Biological, Proteasome Endopeptidase Complex, Protein-Serine-Threonine Kinases, Signal Transduction, Transcription, Genetic, ubiquitin},
	author = {Arteaga, Maria Francisca and Wang, Lin and Ravid, Tommer and Hochstrasser, Mark and Canessa, Cecilia M}
}
