Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator
The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the “master regulator” of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate i...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2017/8093813 |
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| author | Julie E. Morgan Susanna F. Greer |
| author_facet | Julie E. Morgan Susanna F. Greer |
| author_sort | Julie E. Morgan |
| collection | DOAJ |
| description | The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the “master regulator” of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region. Further, CIITA is also modified by degradative K48 polyubiquitination. However, the E3 ligase responsible for these modifications was unknown. We show CIITA ubiquitination and transactivity are enhanced with the histone acetyltransferase (HAT), p300/CBP associated factor (pCAF), and the E3 ligase region within pCAF is necessary for both. Additionally, pCAF mediated ubiquitination is independent of pCAF’s HAT domain, and acetylation deficient CIITA is K48 polyubiquitinated and degraded in the presence of pCAF. Lastly, we identify the histone acetyltransferase, pCAF, as the E3 ligase responsible for CIITA’s ubiquitination. |
| format | Article |
| id | doaj-art-54a4ee1ff3b94c9aa7e372448e67bd0a |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
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| series | International Journal of Cell Biology |
| spelling | doaj-art-54a4ee1ff3b94c9aa7e372448e67bd0a2025-02-03T07:23:51ZengWileyInternational Journal of Cell Biology1687-88761687-88842017-01-01201710.1155/2017/80938138093813Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II TransactivatorJulie E. Morgan0Susanna F. Greer1Division of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30302, USADivision of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30302, USAThe Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the “master regulator” of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region. Further, CIITA is also modified by degradative K48 polyubiquitination. However, the E3 ligase responsible for these modifications was unknown. We show CIITA ubiquitination and transactivity are enhanced with the histone acetyltransferase (HAT), p300/CBP associated factor (pCAF), and the E3 ligase region within pCAF is necessary for both. Additionally, pCAF mediated ubiquitination is independent of pCAF’s HAT domain, and acetylation deficient CIITA is K48 polyubiquitinated and degraded in the presence of pCAF. Lastly, we identify the histone acetyltransferase, pCAF, as the E3 ligase responsible for CIITA’s ubiquitination.http://dx.doi.org/10.1155/2017/8093813 |
| spellingShingle | Julie E. Morgan Susanna F. Greer Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator International Journal of Cell Biology |
| title | Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator |
| title_full | Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator |
| title_fullStr | Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator |
| title_full_unstemmed | Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator |
| title_short | Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator |
| title_sort | pulling a ligase out of a hat pcaf mediates ubiquitination of the class ii transactivator |
| url | http://dx.doi.org/10.1155/2017/8093813 |
| work_keys_str_mv | AT julieemorgan pullingaligaseoutofahatpcafmediatesubiquitinationoftheclassiitransactivator AT susannafgreer pullingaligaseoutofahatpcafmediatesubiquitinationoftheclassiitransactivator |