Ray R B
Department of Internal Medicine, Saint Louis University, Missouri 63110, USA.
Cell Growth Differ. 1995 Sep;6(9):1089-96.
The c-myc promoter binding protein (MBP-1) was identified previously from a human cervical carcinoma cell (HeLa) cDNA expression library (R. Ray and D. M. Miller, Mol. Cell. Biol., 11: 2154-2161, 1991). This study demonstrated that MBP-1 binds to the mouse c-myc P2 TATA box sequences and exerts a negative regulatory role on c-myc transcription. The role of MBP-1 on cell growth was initially examined by transfection of fibroblast cells with MBP-1 cDNA and resulted in rapid cell death. Subsequently, MBP-1 cDNA bearing an inducible promoter was introduced in murine fibroblast cells (NIH3T3) to control the expression of the exogenous MBP-1. Upon induction of exogenous MBP-1 expression, stable transfectants showed reduced c-myc expression, cell death, and DNA fragmentation. To further analyze whether c-myc inhibition mediates or complements the effect of MBP-1, the exogenous MBP-1 when introduced into NIH3T3 cells expressing deregulated human c-myc gene, cell death was interrupted. This study suggested that exogenous expression of MBP-1 induces cell death in fibroblasts by blocking cell proliferation.
c-myc启动子结合蛋白（MBP-1）先前是从人宫颈癌细胞（HeLa）cDNA表达文库中鉴定出来的（R. Ray和D. M. Miller，《分子细胞生物学》，11: 2154 - 2161，1991）。这项研究表明，MBP-1与小鼠c-myc P2 TATA盒序列结合，并对c-myc转录发挥负调控作用。最初通过用MBP-1 cDNA转染成纤维细胞来研究MBP-1对细胞生长的作用，结果导致细胞迅速死亡。随后，将带有可诱导启动子的MBP-1 cDNA导入鼠成纤维细胞（NIH3T3）以控制外源MBP-1的表达。在外源MBP-1表达被诱导后，稳定转染子显示c-myc表达降低、细胞死亡和DNA片段化。为了进一步分析c-myc抑制是介导还是补充MBP-1的作用，当将外源MBP-1导入表达失调的人c-myc基因的NIH3T3细胞时，细胞死亡被阻断。这项研究表明，MBP-1的外源表达通过阻断细胞增殖诱导成纤维细胞死亡。
