PAX5 is the transcriptional activator of mucolipin-2 (MCOLN2) gene.
PAX5 is the transcriptional activator of mucolipin-2 (MCOLN2) gene.
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DOI：
10.1016/j.gene.2014.11.003
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发表时间：
2015-01-25
期刊：
影响因子：
3.5
通讯作者：
Cuajungco MP
中科院分区：
文献类型：
--
作者：
Valadez JA;Cuajungco MP
瞬时受体电位粘脂（TRPML）蛋白属于非选择性阳离子通道的TRP超家族。TRPML 1、TRPML 2和TRPML 3蛋白分别由Mucolipin（MCOLN）-1、MCOLN-2和MCOLN-3基因编码。TRPML 1与IV型粘脂沉积症（MLIV）相关，而没有疾病表型与TRPML 2或-3蛋白相关。TRPML蛋白具有高度的序列相似性，形成异源四聚体，并在膜运输，自噬和金属稳态中发挥作用。先前的研究表明TRPML 2在免疫系统中发挥作用;然而，证据大多是间接的。我们推测，如果TRPML 2参与免疫功能，其表达可能受到免疫相关转录因子蛋白的调控。因此，我们着手确定负责MCOLN 2基因表达的核心启动子区域和转录因子。使用双荧光素酶测定和过表达分析，我们首次揭示了B细胞谱系特异性激活蛋白（BSAP），也称为配对框5（PAX 5），控制MCOLN 2的表达。具体而言，PAX 5在HEK-293细胞中的异源表达显著增加了内源性MCOLN 2转录物和TRPML 2蛋白水平，而靶向内源性PAX 5的RNA干扰降低了其作用。定点突变研究表明，核心启动子和PAX 5结合区位于转录起始位点上游的-79和-60碱基对之间。因此，我们的发现增加了越来越多的TRPML 2可能参与免疫系统的证据。从这项研究中获得的知识可用于进一步表征TRPML 2在B细胞发育和功能中的作用。
Transient Receptor Potential Mucolipin (TRPML) proteins belong to the TRP superfamily of non-selective cation channels. The TRPML1, -2, and -3 proteins are encoded by Mucolipin (MCOLN)-1, -2 and -3 genes, respectively. TRPML1 has been associated with Mucolipidosis type IV (MLIV), while no disease phenotype has been linked with TRPML2 or -3 protein. The TRPML proteins share high sequence similarities, form hetero-tetramers, and serve in membrane trafficking, autophagy, and metal homeostasis. Previous studies suggest that TRPML2 serves a role in the immune system; however, the evidence is mostly indirect. We hypothesize that if TRPML2 is involved in immune function its expression would be likely regulated by an immune-associated transcription factor protein. Thus, we set out to identify the core promoter region and the transcription factor responsible for MCOLN2 gene expression. Using dual-luciferase assay and over-expression analyses, we reveal for the first time that B-cell lineage specific activator protein (BSAP), also known as paired box 5 (PAX5), controls MCOLN2 expression. Specifically, heterologous expression of PAX5 in HEK-293 cells significantly increased endogenous MCOLN2 transcript and TRPML2 protein levels, while RNA interference targeting endogenous PAX5 reduced its effect. Site-directed mutagenesis studies showed that the core promoter and PAX5 binding region to be between -79 and -60 base pairs upstream of the transcriptional start site. Thus, our findings add to a growing list of evidence for TRPML2’s possible involvement in the immune system. The knowledge gained from this study could be used to further characterize the role of TRPML2 in B-cell development and function.
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影响因子：
5.3
作者：
BLAKE, MC;JAMBOU, RC;AZIZKHAN, JC
通讯作者：
AZIZKHAN, JC
DOI：
10.1073/pnas.0709846104
发表时间：
2007-12-04
影响因子：
11.1
作者：
Grimm, Christian;Cuajungco, Math P.;Heller, Stefan
通讯作者：
Heller, Stefan
影响因子：
4.8
作者：
Eichelsdoerfer, Jonathan L.;Evans, Jeffrey A.;Cuajungco, Math P.
通讯作者：
Cuajungco, Math P.
影响因子：
3.6
作者：
Gil, Angel;Maria Aguilera, Concepcion;Canete, Ramon
通讯作者：
Canete, Ramon
影响因子：
4.8
作者：
Collins, Patricia E.;Kiely, Patrick A.;Carmody, Ruaidhri J.
通讯作者：
Carmody, Ruaidhri J.