Interaction and functional collaboration of p300 and C/EBP beta

被引:311
作者
Mink, S [1 ]
Haenig, B [1 ]
Klempnauer, KH [1 ]
机构
[1] MAX PLANCK INST IMMUNBIOL,HANS SPEMANN LAB,D-79108 FREIBURG,GERMANY
关键词
D O I
10.1128/MCB.17.11.6609
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transcriptional coactivators such as p300 and CREB-binding protein (CBP) function as important elements in the transcription factor network, linking individual transactivators via protein-protein interactions to the basal transcriptional machinery. We have investigated whether p300 plays a role in transactivation mediated by C/EBP beta, a conserved member of the C/EBP family. We show that C/EBP beta-dependent transactivation is strongly inhibited by adenovirus E1A but not by E1A mutants defective in p300 binding. Ectopic expression of p300 reverses the E1A-dependent inhibition and increases the transactivation potential of C/EBP beta. Furthermore, we show that C/EBP beta and p300 interact with each other and demonstrate that the sequences responsible for interaction map to the E1A binding region of p300 and the amino terminus of C/EBP beta. Finally, we show that the minimal C/EBP beta binding site of p300 acts as a dominant-negative inhibitor of C/EBP beta. These observations identify p300 as a bona fide coactivator for C/EBP beta. C/EBP beta is highly expressed in the myelomonocytic lineage of the hematopoietic system and cooperates with Myb to activate mim-1, a gene specifically expressed during myelomonocytic differentiation. Recent evidence has shown that Myb recruits CBP (and presumably p300) as a coactivator and, in contrast to C/EBP beta, interacts with the CREB binding site of p300-CBP. We show that p300 not only stimulates the activity of Myb and C/EBP beta individually but also increases the synergy between them. Thus, our results reveal a novel function of p300: in addition to linking specific transcription factors to the basal transcriptional machinery, p300 also mediates the cooperation between transactivators interacting with different domains of p300.
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收藏
页码:6609 / 6617
页数:9
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