The 19S proteasome ATPase Sug1 plays a critical role in regulating MHC class II transcription.
Emerging evidence in yeast suggests roles for ATPases of the 19S proteasome as mediators of transcriptional systems through their association with actively transcribed promoters, facilitation of clearance of paused elongation complexes and recruitment of coactivators. Although 19S subunits also regulate mammalian transcription, their role in recruiting transcription factors remains unclear. Here, we demonstrate for the first time a role for the 19S proteasome ATPase Sug1 in regulating transcription of the critical adaptive immune gene, MHC class II. Sug1 associates with the class II transactivator, CIITA, and with the MHC class II proximal promoter. In the absence of Sug1, HLA-DR promoter activity and MHC class II transcription are decreased. Critically, CIITA association with the MHC II promoter is dramatically decreased when Sug1 expression is reduced, even under conditions of proteasome inhibition. In contrast to the rapid promoter association of the 19S subunit, a 20S proteasome subunit associates with the MHC class II proximal promoter following prolonged cytokine stimulation and its association corresponds with pronounced promoter disassociation of CIITA. Taken together, these data demonstrate that both 19S and 20S subunits of the 26S proteasome play specific and critical roles in regulating CIITA activity and MHC class II transcription.
Bhat
Kavita P
KP
Division of Cellular and Molecular Biology and Physiology, Department of Biology, Georgia State University, Atlanta, Georgia 30302, Atlanta, GA 30302-4010, USA.
Turner
Jonathan D
JD
Myers
Sarah E
SE
Cape
Austin D
AD
Ting
Jenny P-Y
JP
Greer
Susanna F
SF
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D060588:LIM Domain Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; D060588:LIM Domain Proteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C092282:PSMC5 protein, human; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities