ADENOVIRUS-E1A PREVENTS THE RETINOBLASTOMA GENE-PRODUCT FROM COMPLEXING WITH A CELLULAR TRANSCRIPTION FACTOR
ADENOVIRUS-E1A PREVENTS THE RETINOBLASTOMA GENE-PRODUCT FROM COMPLEXING WITH A CELLULAR TRANSCRIPTION FACTOR
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DOI：
10.1038/351494a0
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发表时间：
1991-06-06
期刊：
影响因子：
64.8
通讯作者：
LATHANGUE, NB
中科院分区：
文献类型：
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作者：
BANDARA, LR;LATHANGUE, NB
几种DNA肿瘤病毒的转化蛋白，包括腺病毒E1a和猴病毒40大T抗原，与视网膜母细胞瘤(RB)肿瘤抑制基因产物1，2形成复合体。这需要这些病毒蛋白中必要的区域进行转化，并被认为通过破坏RB蛋白与细胞靶点3的相互作用来使RB蛋白的生长抑制特性失活。事实上，在转化的细胞4中，RB蛋白与E1A和大T抗原形成复合体所需的RB区域经常发生突变。RB蛋白调节增殖的水平尚不清楚，尽管一种可能性是转录。我们之前已经鉴定了一种序列特异性转录因子DRTF1，它的活性随着胚胎癌细胞的分化而下调。DRTF1在几个不同大小但具有相同DNA特异性5，6的离散蛋白复合体(a，b和c)中被发现。我们现在证明其中一个也含有Rb蛋白，进一步，腺病毒E1a蛋白导致Rb蛋白从这个复合体中解离。这需要E1a的保守区域1和2，这是高效转化所必需的。这些结果表明Rb蛋白与DNA结合的转录因子形成一个复合体，并提示Rb蛋白可能通过调节转录来发挥作用。
THE transforming proteins of several DNA tumour viruses, including adenovirus E1a and simian virus 40 large T antigen, complex with the retinoblastoma (Rb) tumour-suppressor gene product 1,2. This requires regions in these viral proteins necessary for transformation and is thought to inactivate the growth-suppressing properties of the Rb protein by disrupting its interaction with cellular targets 3. Indeed, regions of Rb required to form a complex with E1a and large T antigen are often mutated in transformed cells 4. The level at which the Rb protein regulates proliferation is unknown, although one possibility is transcription. We have previously characterized a sequence-specific transcription factor, DRTF1, the activity of which is downregulated as embryonal carcinoma stem cells differentiate. DRTF1 is found in several discrete protein complexes (a, b and c) which are of different sizes but have the same DNA specificity 5,6. We now show that one of these also contains the Rb protein and, further, that the adenovirus E1a protein causes the dissociation of the Rb protein from this complex. This requires conserved regions 1 and 2 of E1a that are known to be required for efficient transformation 7. These results demonstrate that the Rb protein forms a complex with a DNA-bound transcription factor, and suggests that the Rb protein might act by regulating transcription.