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Hematology Reports
Volume 3
Issue 1
10.4081/hr.2011.e5
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Hematology Reports is published by MDPI from Volume 14 Issue 1 (2022). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on mdpi.com as a courtesy and upon agreement with PAGEPress.
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Article

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

by
William Hankey
1,
Matthew Silver
2,
Hong Sun
2,
Terry Zibello
2,
Nancy Berliner
2 and
Arati Khanna-Gupta
2,*
1
Department of Molecular Virology, Immunology & Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
2
Division of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Karp 5212, 1 Balckfan Circle, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Hematol. Rep. 2011, 3(1), e5; https://doi.org/10.4081/hr.2011.e5
Submission received: 16 March 2011 / Revised: 13 May 2011 / Accepted: 13 May 2011 / Published: 20 May 2011

Abstract

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 immunoprecititation in all-trans retinoic acid (ATRA)-inducible promyelocytic cell lines MPRO and NB4. We demonstrate that sumoylated wildtype 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.
Keywords: myeloid transcription; post-translational modification; sumoylation; leukemogenesis myeloid transcription; post-translational modification; sumoylation; leukemogenesis

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MDPI and ACS Style

Hankey, W.; Silver, M.; Sun, H.; Zibello, T.; Berliner, N.; Khanna-Gupta, A. 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. Hematol. Rep. 2011, 3, e5. https://doi.org/10.4081/hr.2011.e5

AMA Style

Hankey W, Silver M, Sun H, Zibello T, Berliner N, Khanna-Gupta A. 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. Hematology Reports. 2011; 3(1):e5. https://doi.org/10.4081/hr.2011.e5

Chicago/Turabian Style

Hankey, William, Matthew Silver, Hong Sun, Terry Zibello, Nancy Berliner, and Arati Khanna-Gupta. 2011. "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" Hematology Reports 3, no. 1: e5. https://doi.org/10.4081/hr.2011.e5

APA Style

Hankey, W., Silver, M., Sun, H., Zibello, T., Berliner, N., & Khanna-Gupta, A. (2011). 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. Hematology Reports, 3(1), e5. https://doi.org/10.4081/hr.2011.e5

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