Houlard Martin, Arudchandran Ramachandran, Regnier-Ricard Fabienne, Germani Antonia, Gisselbrecht Sylvie, Blank Ulrich, Rivera Juan, Varin-Blank Nadine
Unité Inserm 363, Oncologie Cellulaire et Moléculaire, Institut Cochin de Génétique Moléculaire, Hopital Cochin, Paris 75014, France.
J Exp Med. 2002 May 6;195(9):1115-27. doi: 10.1084/jem.20011701.
The importance of the hematopoietic protooncogene Vav1 in immune cell function is widely recognized, although its regulatory mechanisms are not completely understood. Here, we examined whether Vav1 has a nuclear function, as past studies have reported its nuclear localization. Our findings provide a definitive demonstration of Vav1 nuclear localization in a receptor stimulation-dependent manner and reveal a critical role for the COOH-terminal Src homology 3 (SH3) domain and a nuclear localization sequence within the pleckstrin homology domain. Analysis of DNA-bound transcription factor complexes revealed nuclear Vav1 as an integral component of transcriptionally active nuclear factor of activated T cells (NFAT)- and nuclear factor (NF)kappaB-like complexes, and the COOH-terminal SH3 domain as being critical in their formation. Thus, we describe a novel nuclear role for Vav1 as a component and facilitator of NFAT and NFkappaB-like transcriptional activity.
造血原癌基因Vav1在免疫细胞功能中的重要性已得到广泛认可，尽管其调控机制尚未完全明确。此前有研究报道Vav1存在核定位现象，在此我们研究了Vav1是否具有核功能。我们的研究结果明确证实了Vav1以受体刺激依赖的方式进行核定位，并揭示了COOH末端Src同源结构域3（SH3）以及pleckstrin同源结构域内一个核定位序列的关键作用。对与DNA结合的转录因子复合物的分析表明，核Vav1是活化T细胞核因子（NFAT）和核因子（NF）κB样转录活性复合物的一个组成部分，且COOH末端SH3结构域对其形成至关重要。因此，我们描述了Vav1作为NFAT和NFκB样转录活性的一个组成部分和促进因子所具有的一种新的核功能。
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