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Myc-induced SUMOyla...
Myc-induced SUMOylation is a therapeutic vulnerability for B-cell lymphoma.
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Hoellein, Alexander (author)
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Fallahi, Mohammad (author)
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Schoeffmann, Stephanie (author)
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Steidle, Sabine (author)
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Schaub, Franz X (author)
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Rudelius, Martina (author)
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Laitinen, Iina (author)
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- Nilsson, Lisa M, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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Goga, Andrei (author)
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Peschel, Christian (author)
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- Nilsson, Jonas A, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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Cleveland, John L (author)
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Keller, Ulrich (author)
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(creator_code:org_t)
- American Society of Hematology, 2014
- 2014
- English.
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:13, s. 2081-90
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https://europepmc.or...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Myc oncogenic transcription factors (c-Myc, N-Myc, and L-Myc) coordinate the control of cell growth, division, and metabolism. In cancer, Myc overexpression is often associated with aggressive disease, which is in part due to the destruction of select targets by the ubiquitin-proteasome system (eg, SCF(Skp2)-directed destruction of the Cdk inhibitor p27(Kip1)). We reasoned that Myc would also regulate SUMOylation, a related means of posttranslational modification of proteins, and that this circuit would play essential roles in Myc-dependent tumorigenesis. Here, we report marked increases in the expression of genes that encode regulators and components of the SUMOylation machinery in mouse and human Myc-driven lymphomas, resulting in hyper-SUMOylation in these tumors. Further, inhibition of SUMOylation by genetic means disables Myc-induced proliferation, triggering G2/M cell-cycle arrest, polyploidy, and apoptosis. Using genetically defined cell models and conditional expression systems, this response was shown to be Myc specific. Finally, in vivo loss-of-function and pharmacologic studies demonstrated that inhibition of SUMOylation provokes rapid regression of Myc-driven lymphoma. Thus, targeting SUMOylation represents an attractive therapeutic option for lymphomas with MYC involvement.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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- ref (subject category)
- art (subject category)
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Blood
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- By the author/editor
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Hoellein, Alexan ...
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Fallahi, Mohamma ...
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Schoeffmann, Ste ...
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Steidle, Sabine
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Schaub, Franz X
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Rudelius, Martin ...
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show more...
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Laitinen, Iina
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Nilsson, Lisa M, ...
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Goga, Andrei
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Peschel, Christi ...
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Nilsson, Jonas A ...
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Cleveland, John ...
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Keller, Ulrich
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Blood
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University of Gothenburg