Joaquin Manel, Bessa Maria, Saville Mark K, Watson Roger J
Ludwig Institute for Cancer Research, Section of Virology and Cell Biology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 1PG, UK.
Oncogene. 2002 Nov 14;21(52):7923-32. doi: 10.1038/sj.onc.1206001.
B-Myb is a cell-cycle regulated transcription factor which is implicated in cell proliferation and has an essential role in early embryonic development. In this study we examined the functions of B-Myb required to overcome G1 arrest in Saos-2 cells induced by the retinoblastoma-related p107 protein. Our results demonstrated that this activity was independent of B-Myb transactivation function, but correlated with its capacity to form an in vivo complex with p107. A large proportion of B-Myb formed complexes with p107 in cotransfected cells, however, B-Myb bound weakly to the related p130 protein and not at all to pRb. In contrast to the E2F transcription factors, which bind the p107 C-terminal pocket domain, B-Myb recognizes an N-terminal p107 region which overlaps the larger cyclin-binding domain. B-Myb and cyclin A2 formed mutually exclusive complexes with p107, and B-Myb enhanced the activity of co-transfected cyclin E kinase activity, implying that B-Myb affects the cell cycle by preventing sequestration of active cyclin/cdk2 complexes. This study defines a novel function of B-Myb and further suggests that the p107 N-terminus provides an interaction domain for transcription factors involved in cell cycle control.
B-Myb是一种细胞周期调控的转录因子，与细胞增殖有关，在早期胚胎发育中起重要作用。在本研究中，我们检测了B-Myb在克服视网膜母细胞瘤相关p107蛋白诱导的Saos-2细胞G1期阻滞中所需的功能。我们的结果表明，这种活性独立于B-Myb的反式激活功能，但与其在体内与p107形成复合物的能力相关。在共转染细胞中，很大一部分B-Myb与p107形成复合物，然而，B-Myb与相关的p130蛋白结合较弱，与pRb完全不结合。与结合p107 C末端口袋结构域的E2F转录因子不同，B-Myb识别p107的N末端区域，该区域与较大的细胞周期蛋白结合结构域重叠。B-Myb和细胞周期蛋白A2与p107形成相互排斥的复合物，并且B-Myb增强了共转染的细胞周期蛋白E激酶活性，这意味着B-Myb通过阻止活性细胞周期蛋白/cdk2复合物的隔离来影响细胞周期。本研究定义了B-Myb的一种新功能，并进一步表明p107的N末端为参与细胞周期调控的转录因子提供了一个相互作用结构域。
