Nm23-H1 can induce cell cycle arrest and apoptosis in B cells.
Nm23-H1 can induce cell cycle arrest and apoptosis in B cells.
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DOI：
10.4161/cbt.9.12.11995
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发表时间：
2010-06-15
影响因子：
3.6
通讯作者：
Robertson ES
中科院分区：
文献类型：
--
作者：
Choudhuri T;Murakami M;Kaul R;Sahu SK;Mohanty S;Verma SC;Kumar P;Robertson ES
Nm 23-H1是一种已知的肿瘤转移抑制因子，其作为核苷二磷酸激酶，消耗ATP将核苷二磷酸转化为核苷三磷酸。它调节多种细胞活动，包括增殖、发育、迁移和分化，已知是由一系列复杂的信号通路调节的。很少有研究已经解决了在这些细胞过程的背景下，Nm 23-H1的机制作用。为了确定由Nm 23-H1调节的下游通路，我们在伯基特淋巴瘤衍生的B细胞系BJAB中表达Nm 23-H1，并进行通路特异性微阵列分析。表达谱发生显著变化的基因主要集中在调控细胞周期、p53活性和凋亡的基因组中。我们发现细胞周期调节蛋白包括细胞周期蛋白和细胞周期蛋白依赖性激酶抑制剂（抗增殖）的普遍减少，以及凋亡基因包括半胱天冬酶3、9和Bcl-x的上调。nm 23-H1还上调p53和下调p21的表达。真实的时间PCR和启动子分析的结果表明，Nm 23-H1的表达下调细胞周期蛋白D1的剂量响应方式验证了这些基因的数量。此外，我们表明，Nm 23-H1形成一个复杂的细胞转录因子AP 1调节细胞周期蛋白D1的表达水平。表达Nm 23-H1的BJAB细胞表现出降低的增殖率，并且对增加的凋亡敏感，这可能部分是由于Nm 23-H1和p53之间的直接相互作用。这些结果表明，Nm 23-H1可能在调节人B细胞的细胞周期和凋亡中起作用。
Nm23-H1 is a well-known tumor metastasis suppressor, which functions as a nucleoside-diphosphate kinase converting nucleoside diphosphates to nucleoside triphosphates with an expense of ATP. It regulates a variety of cellular activities, including proliferation, development, migration and differentiation known to be modulated by a series of complex signaling pathway. Few studies have addressed the mechanistic action of Nm23-H1 in the context of these cellular processes. To determine the downstream pathways modulated by Nm23-H1, we expressed Nm23-H1 in a Burkitt lymphoma derived B-cell line BJAB and performed pathway specific microarray analysis. The genes with significant changes in expression patterns were clustered in groups which are responsible for regulating cell cycle, p53 activities and apoptosis. We found a general reduction of cell cycle regulatory proteins including cyclins and cyclin dependent kinase inhibitors (anti proliferation), and upregulation of apoptotic genes which included caspase 3, 9 and Bcl-x. Nm23-H1 was also found to upregulate p53 and downregulate p21 expression. A number of these genes were validated by real time PCR and results from promoter assays indicated that Nm23-H1 expression downregulated cyclin D1 in a dose responsive manner. Further, we show that Nm23-H1 forms a complex with the cellular transcription factor AP1 to modulate cyclin D1 expression levels. BJAB cells expressing Nm23-H1 showed reduced proliferation rate and were susceptible to increased apoptosis which may in part be due to a direct interaction between Nm23-H1 and p53. These results suggest that Nm23-H1 may have a role in the regulation of cell cycle and apoptosis in human B-cells.
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影响因子：
5.4
作者：
Kaul, Rajeev;Murakami, Masanao;Robertson, Erle S.
通讯作者：
Robertson, Erle S.
影响因子：
5.4
作者：
Kaul, Rajeev;Murakami, Masanao;Robertson, Erle S.
通讯作者：
Robertson, Erle S.
影响因子：
3.7
作者：
AIELLO, L;GUILFOYLE, R;WEINMANN, R
通讯作者：
WEINMANN, R
影响因子：
5.4
作者：
Kaul, R;Verma, SC;Robertson, ES
通讯作者：
Robertson, ES
影响因子：
8.2
作者：
An, Run;Chu, Yong-lie;Dong, Xiao-ping
通讯作者：
Dong, Xiao-ping