PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells
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- Sung Hoon Cho
- Department of Microbiology & Immunology, Vanderbilt University, Nashville, TN;
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- Shreevrat Goenka
- Department of Microbiology & Immunology, Vanderbilt University, Nashville, TN;
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- Tiina Henttinen
- Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland; and
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- Prathyusha Gudapati
- Department of Microbiology & Immunology, Vanderbilt University, Nashville, TN;
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- Arja Reinikainen
- Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland; and
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- Christine M. Eischen
- Departments of Pathology and
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- Riitta Lahesmaa
- Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland; and
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- Mark Boothby
- Department of Microbiology & Immunology, Vanderbilt University, Nashville, TN;
説明
<jats:p>Poly(ADP-ribos)ylation is one of the longest-known but most enigmatic posttranslational modifications transducing specific signals. The enzyme responsible for the majority of poly(ADP-ribose) polymerization in cells, PARP-1, promotes DNA repair but also mediates a caspase-independent form of apoptosis in response to stressors such as irradiation. However, the biologic function of most other PARPs is not known. Macro-PARPs constitute one branch of the large family of PARP-like proteins also designated as B aggressive lymphoma proteins (BAL1, 2a/2b, 3, or PARP-9, PARP-14, and PARP-15). To elucidate biologic role(s) of a BAL-family macro-PARP, we analyzed mice deficient in PARP-14, a binding partner of the IL-4–induced transcription factor Stat6. We show here that PARP-14 plays a fundamental role mediating protection against apoptosis in IL-4–treated B cells, including that after DNA damage, and mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. Collectively, the results establish that PARP-14 mediates regulation of gene expression and lymphocyte physiology by IL-4 and has a function distinct from PARP-1. Furthermore, the findings suggest mechanisms by which BAL-family proteins might influence pathologic processes involving B lymphocytes.</jats:p>
収録刊行物
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- Blood
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Blood 113 (11), 2416-2425, 2009-03-12
American Society of Hematology