Posttranslational regulation of the NKG2D ligand Mult1 in response to cell stress.
NKG2D is a major stimulatory receptor expressed by natural killer (NK) cells and some T cells. The receptor recognizes major histocompatibility complex class I-like cell surface ligands that are poorly expressed by normal tissues but are often induced in transformed and infected cells. The existence of several NKG2D ligands in each individual, some with strikingly divergent protein sequences, raises the possibility that different ligands are regulated by distinct disease-associated stresses. The transcripts for some ligands, including murine UL16-binding proteinlike transcript 1 (Mult1), are abundant in certain normal tissues where cell surface expression is absent, suggesting the existence of translational or posttranslational regulation. We report here that under normal conditions, Mult1 protein undergoes ubiquitination dependent on lysines in its cytoplasmic tail and lysosomal degradation. Mult1 degradation and ubiquitination is reduced in response to stress imparted by heat shock or ultraviolet irradiation, but not by other forms of genotoxicity, providing a novel mechanism for stress-mediated cellular control of NKG2D ligand expression.
Nice
Timothy J
TJ
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
Coscoy
Laurent
L
Raulet
David H
DH
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000276:immunology*; D054875:Ubiquitination
D002352:Carrier Proteins; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C468260:UL16 binding protein 1, mouse