PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells
PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells
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DOI：
10.1182/blood-2008-03-144121
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发表时间：
2009-03-12
期刊：
影响因子：
20.3
通讯作者：
Boothby, Mark
中科院分区：
文献类型：
--
作者：
Cho, Sung Hoon;Goenka, Shreevrat;Boothby, Mark
聚腺苷二磷酸核糖（Poly（ADP-ribos）ylation）是已知时间最长但最神秘的翻译后修饰之一，其可转导特异性信号。负责细胞中大部分聚（ADP-核糖）聚合的酶PARP-1促进DNA修复，但也介导响应于应激源（如辐射）的半胱天冬酶非依赖性形式的细胞凋亡。然而，大多数其他PARP的生物学功能尚不清楚。大PARP构成PARP样蛋白大家族的一个分支，也称为B侵袭性淋巴瘤蛋白（BAL 1，2a/2 B，3，或PARP-9，PARP-14和PARP-15）。为了阐明BAL-family macro-PARP的生物学作用，我们分析了PARP-14缺陷的小鼠，PARP-14是IL-4诱导的转录因子Stat 6的结合伴侣。我们发现PARP-14在介导IL-4处理的B细胞（包括DNA损伤后的细胞）抗凋亡中发挥重要作用，并介导IL-4对调节细胞存活、增殖和淋巴瘤发生的基因产物水平的影响。总的来说，结果确定PARP-14通过IL-4介导基因表达和淋巴细胞生理学的调节，并且具有不同于PARP-1的功能。此外，研究结果表明BAL-family蛋白可能影响涉及B淋巴细胞的病理过程的机制。（血。2009;113：2416-2425）
Poly(ADP-ribos)ylation is one of the longest-known but most enigmatic post-translational 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. (Blood. 2009;113:2416-2425)