Cathepsin E: a novel target for regulation by class II transactivator.
The aspartic proteinase cathepsin E (CatE) has been implicated in Ag processing. In this study we report that CatE expression is negatively regulated by the MHC class II transactivator (CIITA). CIITA-deficient murine and human B cells expressed greater CatE than wild-type B cells, whereas overexpression of CIITA in a human gastric carcinoma cell line, AGS, resulted in decreased CatE mRNA and protein. AGS cells expressing CIITA also exhibited decreased processing of OVA Ag. Inhibition of CatE expression is specific to the type III CIITA isoform and maps to the acidic and proline/serine/threonine-rich (PST) protein domains of CIITA. We found that CatE expression is inducible by PU.1 and p300, and that this induction can be reversed by CIITA. These findings demonstrate a novel phenomenon: regulation of CatE Ag processing by CIITA in an isoform-dependent manner.
Yee
Christina S K
CS
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yao
Yongxue
Y
Li
Ping
P
Klemsz
Michael J
MJ
Blum
Janice S
JS
Chang
Cheong-Hee
CH
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D020059:Cathepsin E / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D050881:E1A-Associated p300 Protein; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000235:genetics; D004794:Enzyme Repression; D016147:Genes, Tumor Suppressor; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
D020059:Cathepsin E; D050881:E1A-Associated p300 Protein; D004792:Enzyme Precursors; D007527:Isoenzymes; D009687:Nuclear Proteins; D010047:Ovalbumin; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C083728:MHC class II transactivator protein; C494361:Ep300 protein, mouse