Homer-3 regulates activation of serum response element in T cells via its EVH1 domain
Homer-3 regulates activation of serum response element in T cells via its EVH1 domain
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DOI：
10.1182/blood-2003-08-2671
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发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Xavier, R
中科院分区：
文献类型：
--
作者：
Ishiguro, K;Xavier, R
果蝇激活/血管舒张刺激磷蛋白（Ena/VASP）同源1（EVH 1）结构域蛋白调节神经元和免疫突触的信号转导。尽管在这些突触上共享细胞生物机制，但将突触活动传递到细胞核的客户蛋白的调节可能是不同的。Homer-3是EVH 1家族的成员，在胸腺中表达，表明该蛋白在T细胞信号转导中的作用。在T细胞受体（TCR）接合后，Homer-3在肌动蛋白积累之前被募集到Jurkat细胞与抗CD 3和CD 28抗体包被的珠粒的接触区域，并且随后易位到细胞核中。Homer-3的过表达通过血清应答元件（SRE）降低了对抗CD 3抗体、佛波酯或显性活性Ha-Ras的应答中的转录激活。与这些结果一致，Homer-3的敲低增加了SRE活化。Homer-3与CCAAT/增强子结合蛋白β（C/EBP β）共沉淀，CCAAT/增强子结合蛋白β是结合SRE的转录因子之一，并且具有与EVH 1结构域结合的共有基序。此外，Homer-3及其EVH 1结构域片段降低了C/EBP β的转录激活。这些发现表明，Homer-3可能通过其EVH 1结构域与C/EBP β之间的相互作用参与调节T细胞中SRE活化。(C)2004年，美国血液学会。
Drosophila enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) homology 1 (EVH1) domain proteins regulate signal transduction at the neuronal and immunologic synapse. Despite shared cell biologic machinery at these synapses, the regulation of client proteins that transmit synaptic activity to the nucleus is likely to be different. Homer-3, a member of the EVH1 family, is expressed in the thymus, suggesting a role for this protein in T-cell signal transduction. Upon T-cell receptor (TCR) engagement, Homer-3 was recruited to the contact area of Jurkat cells to anti-CD3 and CD28 antibody-coated beads prior to actin accumulation and was subsequently translocated into the nucleus. Overexpression of Homer-3 reduced transcriptional activation via the serum response element (SRE) in response to anti-CD3 antibody, phorbol ester, or dominant active Ha-Ras. Consistent with these results, knockdown of Homer-3 increased SRE activation. Homer-3 coprecipitated with CCAAT/enhancer binding protein beta (C/EBPbeta), one of the transcription factors that binds to the SRE and has a consensus motif binding to EVH1 domain. Moreover, Homer-3 and its EVH1 domain fragment reduced transcriptional activation of C/EBPbeta. These findings suggest that Homer-3 may be involved in the regulation of SRE activation in T cells via interaction between its EVH1 domain and C/EBPbeta. (C) 2004 by The American Society of Hematology.