Dou Q P, Markell P J, Pardee A B
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3256-60. doi: 10.1073/pnas.89.8.3256.
Transcription of the murine thymidine kinase gene, which is coregulated with the G1/S phase transition, is activated by changing the binding of protein complexes Yi1 and Yi2 to three upstream DNA motifs. Yi1 is replaced by Yi2 shortly before S phase. Yi1 contains a protein of 110 kDa that binds to the DNA motif sites and may be an underphosphorylated murine retinoblastoma protein, shown by its molecular mass, timing of its activity, and antibody recognition. An H1 kinase related to cdc2 cofractionates with both complexes. We propose that this kinase phosphorylates the murine retinoblastoma protein, releasing transcriptional inhibitions by Yi1 and permitting cell cycle progression. These results provide a cycle-related molecular target for such complexes. They are based on investigations of cycle control in uninfected cells. The Yi complexes are similar but not identical to complexes that include a cellular protein, E2F, that was originally found to bind to adenovirus DNA.
鼠胸苷激酶基因的转录与G1/S期转换协同调控，通过改变蛋白复合物Yi1和Yi2与三个上游DNA基序的结合而被激活。在S期前不久，Yi1被Yi2取代。Yi1包含一个110 kDa的蛋白质，它与DNA基序位点结合，根据其分子量、活性时间和抗体识别情况，可能是一种低磷酸化的鼠视网膜母细胞瘤蛋白。一种与cdc2相关的H1激酶与这两种复合物共分离。我们提出这种激酶使鼠视网膜母细胞瘤蛋白磷酸化，解除Yi1的转录抑制作用并允许细胞周期进程。这些结果为这类复合物提供了一个与细胞周期相关的分子靶点。它们基于对未感染细胞中细胞周期调控的研究。Yi复合物与包含一种最初发现可结合腺病毒DNA的细胞蛋白E2F的复合物相似但并不相同。
