Nead M A, Baglia L A, Antinore M J, Ludlow J W, McCance D J
Departments of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
EMBO J. 1998 Apr 15;17(8):2342-52. doi: 10.1093/emboj/17.8.2342.
The retinoblastoma protein (Rb) acts as a critical cell-cycle regulator and loss of Rb function is associated with a variety of human cancer types. Here we report that Rb binds to members of the AP-1 family of transcription factors, including c-Jun, and stimulates c-Jun transcriptional activity from an AP-1 consensus sequence. The interaction involves the leucine zipper region of c-Jun and the B pocket of Rb as well as a C-terminal domain. We also present evidence that the complexes are found in terminally differentiating keratinocytes and cells entering the G1 phase of the cell cycle after release from serum starvation. The human papillomavirus type 16 E7 protein, which binds to both c-Jun and Rb, inhibits the ability of Rb to activate c-Jun. The results provide evidence of a role for Rb as a transcriptional activator in early G1 and as a potential modulator of c-Jun expression during keratinocyte differentiation.
视网膜母细胞瘤蛋白(Rb)是一种关键的细胞周期调节因子,Rb功能的丧失与多种人类癌症类型相关。在此我们报告,Rb与转录因子AP-1家族的成员(包括c-Jun)结合,并从AP-1共有序列刺激c-Jun转录活性。这种相互作用涉及c-Jun的亮氨酸拉链区域、Rb的B口袋以及一个C末端结构域。我们还提供证据表明,在终末分化的角质形成细胞和从血清饥饿释放后进入细胞周期G1期的细胞中发现了这些复合物。人乳头瘤病毒16型E7蛋白,它与c-Jun和Rb都结合,抑制Rb激活c-Jun的能力。这些结果为Rb在G1早期作为转录激活因子以及在角质形成细胞分化过程中作为c-Jun表达的潜在调节因子的作用提供了证据。