C-MYC AND BCL-2 MODULATE P53 FUNCTION BY ALTERING P53 SUBCELLULAR TRAFFICKING DURING THE CELL-CYCLE
C-MYC AND BCL-2 MODULATE P53 FUNCTION BY ALTERING P53 SUBCELLULAR TRAFFICKING DURING THE CELL-CYCLE
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DOI：
10.1073/pnas.91.13.5878
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发表时间：
1994-06-21
影响因子：
11.1
通讯作者：
CLARKE, MF
中科院分区：
文献类型：
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作者：
RYAN, JJ;PROCHOWNIK, E;CLARKE, MF
我们已经研究了c-myc和bcl-2癌基因调节p53功能的能力。我们的研究表明，人Bcl-2蛋白和p53蛋白的同时表达可降低小鼠红白血病细胞的存活率。这种效应与p53介导的细胞周期阻滞的G（1）特异性丧失有关。此外，我们发现c-myc和bcl-2基因协同抑制p53功能。bcl-2和c-myc的共表达可以通过改变p53在细胞周期中的亚细胞运输来完全克服p53诱导的细胞凋亡和细胞周期停滞：在GI的关键时期，p53保留在共转染细胞的细胞质中。这一发现表明，正常造血祖细胞可以生存和增殖，尽管p53的表达和bcl-2和c-myc的不适当的表达可以在转化中合作的机制。
We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. This effect was associated with a loss of the G(1) specificity of p53-mediated cell cycle arrest. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in GI. This finding suggests a mechanism by which normal hematopoietic progenitors can survive and proliferate despite p53 expression and by which the inappropriate expression of bcl-2 and c-myc can cooperate in transformation.