Dagnino L, Zhu L, Skorecki K L, Moses H L
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Cell Growth Differ. 1995 Feb;6(2):191-8.
The Rb family of proteins includes pRb, p107, and p130. These nuclear polypeptides associate with cyclins and transcription factors involved in the control of cell proliferation. This has suggested that members of the pRb family may modulate cell growth, at least in part, by regulating gene transcription. We have investigated the ability of p107 to modulate transcription and compared it with that of pRb. Whereas pRb inhibition of the c-myc promoter required the presence of E2F sites, p107 inhibition did not. Moreover, p107, but not pRb, repressed transcription from other promoters including fibronectin, herpes virus thymidine kinase, and a synthetic promoter containing a SV40 repeat activator motif upstream from the adenovirus major late-promoter TATA box. In contrast, the activity of the TATA-lacking promoters from the epidermal growth factor receptor and the cytoplasmic phospholipase A2 genes was unaffected by either p107 or pRb. Likewise, overexpression of p107 or pRb had no effect on the activity of a synthetic promoter lacking a TATA box and containing the SV40 repeat motif upstream from the terminal transferase gene initiator element. The domains in p107 required for transcriptional repression included the A segment of the pocket region and parts of the B segment, but not the spacer domain. In spite of their structural similarities, p107 and pRb may contribute to the control of cell proliferation by modulating the transcription of different genes.
Rb蛋白家族包括pRb、p107和p130。这些核多肽与参与细胞增殖控制的细胞周期蛋白和转录因子相关联。这表明pRb家族成员可能至少部分地通过调节基因转录来调控细胞生长。我们研究了p107调节转录的能力，并将其与pRb的能力进行了比较。pRb对c-myc启动子的抑制需要E2F位点的存在，而p107的抑制则不需要。此外，p107而非pRb抑制包括纤连蛋白、疱疹病毒胸苷激酶以及在腺病毒主要晚期启动子TATA框上游含有SV40重复激活基序的合成启动子的转录。相反，表皮生长因子受体和细胞质磷脂酶A2基因缺乏TATA框的启动子活性不受p107或pRb的影响。同样，p107或pRb的过表达对缺乏TATA框且在末端转移酶基因起始元件上游含有SV40重复基序的合成启动子的活性没有影响。p107转录抑制所需的结构域包括口袋区域的A段和B段的部分，但不包括间隔结构域。尽管p107和pRb在结构上有相似性，但它们可能通过调节不同基因的转录来参与细胞增殖的控制。
