Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain J P, Troalen F, Trouche D, Harel-Bellan A
Laboratoire Oncogénèse, Différenciation et Transduction du Signal, CNRS UPR 9079, Villejuif, France.
Nature. 1998 Feb 5;391(6667):601-5. doi: 10.1038/35410.
The retinoblastoma tumour-suppressor protein Rb inhibits cell proliferation by repressing a subset of genes that are controlled by the E2F family of transcription factors and which are involved in progression from the G1 to the S phase of the cell cycle. Rb, which is recruited to target promoters by E2F1, represses transcription by masking the E2F1 transactivation domain and by inhibiting surrounding enhancer elements, an active repression that could be crucial for the proper control of progression through the cell cycle. Some transcriptional regulators act by acetylating or deacetylating the tails protruding from the core histones, thereby modulating the local structure of chromatin: for example, some transcriptional repressors function through the recruitment of histone deacetylases. We show here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb. In HDAC1, the sequence involved is an LXCXE motif, similar to that used by viral transforming proteins to contact Rb. Our results strongly suggest that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.
视网膜母细胞瘤肿瘤抑制蛋白Rb通过抑制由E2F转录因子家族控制且参与细胞周期从G1期到S期进程的一部分基因，来抑制细胞增殖。Rb由E2F1募集至靶启动子，通过掩盖E2F1反式激活结构域并抑制周围增强子元件来抑制转录，这种主动抑制对于细胞周期进程的恰当控制可能至关重要。一些转录调节因子通过使核心组蛋白伸出的尾部乙酰化或去乙酰化来发挥作用，从而调节染色质的局部结构：例如，一些转录抑制因子通过募集组蛋白去乙酰化酶发挥功能。我们在此表明，组蛋白去乙酰化酶HDAC1与Rb发生物理相互作用并协同作用。在HDAC1中，所涉及的序列是一个LXCXE基序，类似于病毒转化蛋白用于与Rb接触的基序。我们的结果有力地表明，Rb/HDAC1复合物是细胞增殖和分化控制中的关键元件，并且它可能是转化病毒的作用靶点。
