Baas Roy, van Teeffelen Hetty A A M, Tjalsma Sjoerd J D, Timmers H Th Marc
a Molecular Cancer Research and Stem Cells, Regenerative Medicine Center, Center for Molecular Medicine , University Medical Center Utrecht , Utrecht , The Netherlands.
Transcription. 2018;9(2):67-74. doi: 10.1080/21541264.2017.1373890. Epub 2017 Nov 3.
Sma and Mad related (SMAD)-mediated Transforming Growth Factor β (TGF-β) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-β-activated SMAD signaling. We immunoprecipitated PTIP and PA1 with all SMAD family members to identify the TGF-β and not BMP-specific SMADs as interacting proteins. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-β-specific genes to be regulated by the MLL4 complex, which links TGF-β signaling to transcription regulation by the MLL4 methyltransferase complex.
与Sma和Mad相关的（SMAD）介导的转化生长因子β（TGF-β）和骨形态发生蛋白（BMP）信号传导是各种细胞过程所必需的。活化的异源三聚体SMAD蛋白复合物与核蛋白如组蛋白乙酰转移酶p300、PCAF以及混合谱系白血病4（MLL4）亚基Pax反式激活结构域相互作用蛋白（PTIP）结合，以调节基因转录。我们研究了PTIP和PTIP相互作用蛋白1（PA1）在与TGF-β激活的SMAD信号传导相关方面的功能作用。我们用所有SMAD家族成员免疫沉淀PTIP和PA1，以鉴定作为相互作用蛋白的TGF-β而非BMP特异性SMAD。MLL4以及亚基PA1和PTIP的基因沉默实验证实，TGF-β特异性基因受MLL4复合物调控，该复合物将TGF-β信号传导与MLL4甲基转移酶复合物的转录调控联系起来。
