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Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias

In this study, we have examined the role of post-translational modification of the myeloid master regulator C/EBPα by small ubiquitin-related modifier (SUMO). We have used transient transfection analysis, oligonucleotide pulldown assays and chromatin immuno-precititation in all-trans retinoic acid (...

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Autores principales: Hankey, William, Silver, Matthew, Sun, B.S.Hong, Zibello, Terry, Berliner, Nancy, Khanna-Gupta, Arati
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238474/
https://www.ncbi.nlm.nih.gov/pubmed/22184527
http://dx.doi.org/10.4081/hr.2011.e5
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author Hankey, William
Silver, Matthew
Sun, B.S.Hong
Zibello, Terry
Berliner, Nancy
Khanna-Gupta, Arati
author_facet Hankey, William
Silver, Matthew
Sun, B.S.Hong
Zibello, Terry
Berliner, Nancy
Khanna-Gupta, Arati
author_sort Hankey, William
collection PubMed
description In this study, we have examined the role of post-translational modification of the myeloid master regulator C/EBPα by small ubiquitin-related modifier (SUMO). We have used transient transfection analysis, oligonucleotide pulldown assays and chromatin immuno-precititation in all-trans retinoic acid (ATRA)-inducible promyelocytic cell lines MPRO and NB4. We demonstrate that sumoylated wild-type p42-C/EBPα is associated with negative regulation of the myeloid specific lactoferrin (LF) gene in early myeloid cells and that a reduction in p42-C/EBPα sumoylation coincides with expression of the LF gene in maturing myeloid cells. In the acute promyelocytic leukemia cell line NB4 however, sumoylated p42 remains persistently bound to the LF promoter following ATRA-induction. This correlates with lack of lactoferrin expression in these cells. Changes in sumoylation status of C/EBPα thus appear to contribute to a switch that regulates transcriptional activity of this master regulator during normal neutrophil development. We also demonstrate that sumoylation of the AML associated dominant negative p30-C/EBPα isoform does not alter transactivation activity of the LF promoter. This may be because the p30 C/EBPα isoform binds to the LF promoter much less efficiently than its full length counterpart. Our data suggest that the activity of p42-C/EBPα in the developing neutrophil is more sensitive to changes in sumoylation than the p30 isoform. This difference may contribute to the leukemogenic potential of p30-C/EBPα.
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spelling pubmed-32384742011-12-19 Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias Hankey, William Silver, Matthew Sun, B.S.Hong Zibello, Terry Berliner, Nancy Khanna-Gupta, Arati Hematol Rep Article In this study, we have examined the role of post-translational modification of the myeloid master regulator C/EBPα by small ubiquitin-related modifier (SUMO). We have used transient transfection analysis, oligonucleotide pulldown assays and chromatin immuno-precititation in all-trans retinoic acid (ATRA)-inducible promyelocytic cell lines MPRO and NB4. We demonstrate that sumoylated wild-type p42-C/EBPα is associated with negative regulation of the myeloid specific lactoferrin (LF) gene in early myeloid cells and that a reduction in p42-C/EBPα sumoylation coincides with expression of the LF gene in maturing myeloid cells. In the acute promyelocytic leukemia cell line NB4 however, sumoylated p42 remains persistently bound to the LF promoter following ATRA-induction. This correlates with lack of lactoferrin expression in these cells. Changes in sumoylation status of C/EBPα thus appear to contribute to a switch that regulates transcriptional activity of this master regulator during normal neutrophil development. We also demonstrate that sumoylation of the AML associated dominant negative p30-C/EBPα isoform does not alter transactivation activity of the LF promoter. This may be because the p30 C/EBPα isoform binds to the LF promoter much less efficiently than its full length counterpart. Our data suggest that the activity of p42-C/EBPα in the developing neutrophil is more sensitive to changes in sumoylation than the p30 isoform. This difference may contribute to the leukemogenic potential of p30-C/EBPα. PAGEPress Publications 2011-05-20 /pmc/articles/PMC3238474/ /pubmed/22184527 http://dx.doi.org/10.4081/hr.2011.e5 Text en ©Copyright W. Hankey et al., 2011 This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). Licensee PAGEPress, Italy
spellingShingle Article
Hankey, William
Silver, Matthew
Sun, B.S.Hong
Zibello, Terry
Berliner, Nancy
Khanna-Gupta, Arati
Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias
title Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias
title_full Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias
title_fullStr Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias
title_full_unstemmed Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias
title_short Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias
title_sort differential effects of sumoylation on the activities of ccaat enhancer binding protein alpha (c/ebpα) p42 versus p30 may contribute in part, to aberrant c/ebpα activity in acute leukemias
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238474/
https://www.ncbi.nlm.nih.gov/pubmed/22184527
http://dx.doi.org/10.4081/hr.2011.e5
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