HBP1: A HMG box transcriptional repressor that is targeted by the retinoblastoma family
HBP1: A HMG box transcriptional repressor that is targeted by the retinoblastoma family
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DOI：
10.1101/gad.11.3.383
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发表时间：
1997-02-01
影响因子：
10.5
通讯作者：
Yee, AS
中科院分区：
文献类型：
--
作者：
Tevosian, SG;Shih, HH;Yee, AS
细胞分化的一个显著特征是在视网膜母细胞瘤（RB）家族（RB、p130、p107）的复杂参与下启动并维持不可逆的细胞周期停滞。我们已分离出HBP1转录抑制因子，它是分化细胞中RB家族的一个潜在靶点。通过同源性分析，HBP1是一种序列特异性的高迁移率族（HMG）转录因子，其中LEE - I是特征最为明确的家族成员。HBP1的几个特性表明它在分化细胞中作为转录和细胞周期调节因子具有有趣的作用。首先，对HBP1蛋白序列的检测揭示了两个一致的RB相互作用基序（LXCXE和IXCXE）。其次，HBP1选择性地与RB和p130相互作用，而不与p107相互作用。HBP1、RB和p130的水平都随着分化而上调；相反，p107的水平下降。第三，HBP1可作为N - MYC启动子的转录抑制因子发挥作用，N - MYC是一个关键的细胞周期和发育基因。第四，由于在细胞周期循环的细胞中N - MYC启动子的激活需要E2F转录因子，我们表明E2F - 1和HBP1代表相反的转录信号，它们可以在N - MYC启动子内整合。第五，HBP1的表达导致有效的细胞周期停滞。在存在最佳增殖信号的情况下也表现出停滞表型，这表明HBP1发挥着主导的调节作用。综上所述，这些结果表明HBP1可能代表一种独特的转录抑制因子，在分化过程中细胞周期停滞的启动和建立中起作用。
A prominent feature of cell differentiation is the initiation and maintenance of an irreversible cell cycle arrest with the complex involvement of the retinoblastoma (RE) family (RE, p130, p107). We have isolated the HBP1 transcriptional repressor as a potential target of the RE family in differentiated cells. By homology, HBP1 is a sequence-specific HMG transcription factor, of which LEE-I is the best-characterized family member. Several features of HBP1 suggest an intriguing role as a transcriptional and cell cycle regulator in differentiated cells. first, inspection of the HBP1 protein sequence revealed two consensus RE interaction motifs (LXCXE and IXCXE). Second, HBP1 interaction was selective for RE and p130, but not p107. HBP1, RE, and p130 levels are all up-regulated with differentiation; in contrast, p107 levels decline. Third, HBP1 can function as a transcriptional repressor of the promoter for N-MYC, which is a critical cell cycle and developmental gene. fourth, because the activation of the N-MYC promoter in cycling cells required the E2F transcription factor, we show that E2F-1 and HBP1 represent opposite transcriptional signals that can be integrated within the N-MYC promoter. Fifth, the expression of HBP1 lead to efficient cell cycle arrest. The arrest phenotype was manifested in the presence of optimal proliferation signals, suggesting that HBP1 exerted a dominant regulatory role. Taken together, the results suggest that HBP1 may represent a unique transcriptional repressor with a role in initiation and establishment of cell cycle arrest during differentiation.