TRAF6 activation in multiple myeloma: a potential therapeutic target.
TRAF6 activation in multiple myeloma: a potential therapeutic target.
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DOI：
10.1016/j.clml.2012.01.006
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Bonavida B
中科院分区：
文献类型：
--
作者：
Liu H;Tamashiro S;Baritaki S;Penichet M;Yu Y;Chen H;Berenson J;Bonavida B
多发性骨髓瘤 (MM) 是一种无法治愈的 B 淋巴细胞恶性肿瘤。在过去的几年里，新的治疗选择已经出现；然而，几乎所有患者都会对目前可用的治疗药物产生耐药性。 MM的发病机制和化疗耐药机制包括遗传异常、染色体易位、基因突变、MM细胞与骨髓微环境之间的相互作用以及凋亡信号通路的缺陷。与MM和骨髓基质细胞发病机制相关的生存信号通路在促进生长、存活、粘附、永生化、血管生成和耐药性方面发挥着至关重要的作用。核因子-κB受体激活剂/核因子-κB受体激活剂配体/肿瘤坏死因子受体相关因子(RANK/RANKL-TRAF6)信号通路通过激活破骨细胞前体细胞中的NF-κB和Janus激酶/信号转导器和转录激活剂(JNK)通路介导溶骨性骨病变，从而介导溶骨性骨病变。 导致骨病的主要临床表现。 TRAF6 还被确定为 Akt 泛素化和膜募集及其在生长因子刺激下磷酸化的连接酶。通过沉默 RNA 或诱饵肽抑制 TRAF6 可减少 MM 肿瘤细胞增殖并增加细胞凋亡和骨吸收。一些蛋白酶体抑制剂和苯并恶二唑衍生物对TRAF6的活性和功能表现出抑制作用。总的来说，我们建议 TRAF6 可以被视为治疗 MM 的潜在治疗靶点。
Multiple myeloma (MM) is an incurable B-lymphocyte malignancy. New therapeutic options have become available during the past several years; however nearly all patients acquire resistance to currently available therapeutic agents. Mechanisms contributing to the pathogenesis and chemoresistance of MM include genetic abnormalities, chromosomal translocations, gene mutations, the interaction between MM cells and the bone marrow microenvironment, and defects in the apoptotic signaling pathways. Survival signaling pathways associated with the pathogenesis of MM and bone marrow stromal cells play crucial roles in promoting growth, survival, adhesion, immortalization, angiogenesis, and drug resistance. The receptor activator of nuclear factor-kappa B/receptor activator of nuclear factor-kappa B ligand/tumor necrosis factor receptor-associated factor (RANK/RANKL-TRAF6) signal pathway mediates osteolytic bone lesions through the activation of the NF-κB and Janus kinase/signal transducer and activator of transcription (JNK) pathways in osteoclast precursor cells and thus contributes to the main clinical manifestations of bone disease. TRAF6 has also been identified as a ligase for Akt ubiquitination and membrane recruitment and its phosphorylation on growth factor stimulation. The inhibition of TRAF6 by silencing RNA or by decoy peptides decreases MM tumor cell proliferation and increases apoptosis as well as bone resorption. Some proteasome inhibitors and benzoxadiazole derivatives showed inhibitory effects on the activity and function of TRAF6. Overall, we propose that TRAF6 may be considered as a potential therapeutic target for the treatment of MM.
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影响因子：
20.3
作者：
Giuliani, N;Bataille, R;Barillé, S
通讯作者：
Barillé, S
DOI：
10.1073/pnas.0404132101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Ea, CK;Sun, L;Chen, ZJJ
通讯作者：
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影响因子：
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作者：
通讯作者：
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影响因子：
2.7
作者：
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通讯作者：
Hou Han
影响因子：
20.3
作者：
Giuliani, N;Colla, S;Rizzoli, V
通讯作者：
Rizzoli, V