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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-2-5
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pubmed:abstractText |
Oncogenic c-Myc is known to balance excessive proliferation by apoptosis that can be triggered by p53-dependent and p53-independent signaling networks. Here, we provide evidence that the BH3-only proapoptotic Bcl-2 family members Bcl-2 modifying factor (Bmf) and Bcl-2 antagonist of cell death (Bad) are potent antagonists of c-Myc-driven B-cell lymphomagenesis. Tumor formation was preceded by the accumulation of preneoplastic pre-B and immature immunoglobulin M-positive (IgM(+)) B cells in hematopoietic organs of Emu-myc/bmf(-/-) mice, whereas Emu-myc/bad(-/-) mice showed an increase of pre-B cells limited to the spleen. Although the loss of Bad had no impact on the tumor immunophenotype, Bmf deficiency favored the development of IgM(+) B cell over pre-B cell tumors. This phenomenon was caused by a strong protection of immature IgM(+) B cells from oncogene-driven apoptosis caused by loss of bmf and c-Myc-induced repression of Bmf expression in premalignant pre-B cells. Steady-state levels of B-cell apoptosis also were reduced in the absence of Bad, in support of its role as a sentinel for trophic factor-deprivation. Loss of Bmf reduced the pressure to inactivate p53, whereas Bad deficiency did not, identifying Bmf as a novel component of the p53-independent tumor suppressor pathway triggered by c-Myc.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Bad protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bmf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myc protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
4
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pubmed:volume |
115
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
995-1005
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pubmed:dateRevised |
2011-4-6
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pubmed:meshHeading |
pubmed-meshheading:19965635-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:19965635-Animals,
pubmed-meshheading:19965635-Apoptosis,
pubmed-meshheading:19965635-B-Lymphocytes,
pubmed-meshheading:19965635-Blotting, Western,
pubmed-meshheading:19965635-Female,
pubmed-meshheading:19965635-Lymphoma,
pubmed-meshheading:19965635-Male,
pubmed-meshheading:19965635-Mice,
pubmed-meshheading:19965635-Mice, Inbred C57BL,
pubmed-meshheading:19965635-Mice, Knockout,
pubmed-meshheading:19965635-Mice, Transgenic,
pubmed-meshheading:19965635-Precancerous Conditions,
pubmed-meshheading:19965635-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:19965635-Spleen,
pubmed-meshheading:19965635-Survival Analysis,
pubmed-meshheading:19965635-Time Factors,
pubmed-meshheading:19965635-Tumor Burden,
pubmed-meshheading:19965635-Tumor Suppressor Protein p53,
pubmed-meshheading:19965635-bcl-Associated Death Protein
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pubmed:year |
2010
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pubmed:articleTitle |
Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad.
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pubmed:affiliation |
Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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