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Rb与c-Jun结合并激活转录。

Rb binds c-Jun and activates transcription.

作者信息

Nead M A, Baglia L A, Antinore M J, Ludlow J W, McCance D J

机构信息

Departments of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.

出版信息

EMBO J. 1998 Apr 15;17(8):2342-52. doi: 10.1093/emboj/17.8.2342.

DOI:10.1093/emboj/17.8.2342
PMID:9545246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1170577/
Abstract

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.

摘要

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。

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1
Rb binds c-Jun and activates transcription.Rb与c-Jun结合并激活转录。
EMBO J. 1998 Apr 15;17(8):2342-52. doi: 10.1093/emboj/17.8.2342.
2
Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes.显性负性Jun的表达可抑制升高的AP-1和NF-κB反式激活,并抑制人乳头瘤病毒永生化人角质形成细胞的锚定非依赖性生长。
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本文引用的文献

1
Differential phosphorylation of the retinoblastoma protein by G1/S cyclin-dependent kinases.G1/S 细胞周期蛋白依赖性激酶对视网膜母细胞瘤蛋白的差异性磷酸化作用
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Induction of apoptosis by the transcription factor c-Jun.转录因子c-Jun诱导细胞凋亡
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Monoclonal antibodies specific for underphosphorylated retinoblastoma protein identify a cell cycle regulated phosphorylation site targeted by CDKs.针对低磷酸化视网膜母细胞瘤蛋白的单克隆抗体识别出细胞周期蛋白依赖性激酶(CDKs)靶向的一个细胞周期调节磷酸化位点。
Oncogene. 1997 Jan 16;14(2):249-54. doi: 10.1038/sj.onc.1200824.
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Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs.视网膜母细胞瘤蛋白通过与C/EBPs直接相互作用正向调节终末脂肪细胞分化。
Genes Dev. 1996 Nov 1;10(21):2794-804. doi: 10.1101/gad.10.21.2794.
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The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors.人乳头瘤病毒16型E7基因产物与转录因子AP1家族相互作用并对其进行反式激活。
EMBO J. 1996 Apr 15;15(8):1950-60.
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Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6.视网膜母细胞瘤蛋白直接与转录因子NF-IL6相互作用并激活它。
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):465-9. doi: 10.1073/pnas.93.1.465.
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Regulated expression of the retinoblastoma gene in differentiating embryonal carcinoma cells.视网膜母细胞瘤基因在分化的胚胎癌细胞中的调控表达。
Oncogene. 1993 Jun;8(6):1585-91.
8
AP-1 activity during normal human keratinocyte differentiation: evidence for a cytosolic modulator of AP-1/DNA binding.正常人类角质形成细胞分化过程中的AP-1活性:AP-1/DNA结合的胞质调节剂的证据。
Exp Cell Res. 1993 Jan;204(1):136-46. doi: 10.1006/excr.1993.1018.
9
Heterodimer formation of cJun and ATF-2 is responsible for induction of c-jun by the 243 amino acid adenovirus E1A protein.cJun与ATF-2形成异源二聚体,这是243个氨基酸的腺病毒E1A蛋白诱导c-jun产生的原因。
EMBO J. 1993 Feb;12(2):479-87. doi: 10.1002/j.1460-2075.1993.tb05680.x.
10
Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation.生肌因子与视网膜母细胞瘤蛋白的相互作用介导肌肉细胞的定向分化。
Cell. 1993 Feb 12;72(3):309-24. doi: 10.1016/0092-8674(93)90110-c.