Activation of the unfolded protein response and alternative splicing of ATF6alpha in HLA-B27 positive lymphocytes.
Misfolding of major histocompatibility complex (MHC) class I molecules has been implicated in the rheumatic autoimmune disease ankylosing spondylitis (AS), and has been linked to the unfolded protein response (UPR) in rodent AS models. XBP1 and ATF6alpha are two important transcription factors that initiate and co-ordinate the UPR. Here we show that misoxidised MHC class I heavy chains activate XBP1 processing in a similar manner to tunicamycin, with tunicamycin and dithiothreitol (DTT) inducing differential XBP1 processing. Unexpectedly, ATF6alpha mRNA is alternatively spliced during reducing stress in lymphocytes. This shorter ATF6alpha message lacks exon 7 and may have a regulatory role in the UPR.
Lemin
Andrew J
AJ
School of Biological and Biomedical Sciences, University of Durham, South Road, Durham DH1 3LE, England, United Kingdom.
Saleki
Khalil
K
van Lith
Marcel
M
Benham
Adam M
AM
D051702:Activating Transcription Factor 6 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D000071701:Regulatory Factor X Transcription Factors; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology; D000071717:X-Box Binding Protein 1
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D004268:DNA-Binding Proteins; D015796:HLA-B27 Antigen; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D014415:Tunicamycin; D004229:Dithiothreitol