Nguyen T O, Capra J D, Sontheimer R D
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Mol Immunol. 1996 Mar-Apr;33(4-5):379-86. doi: 10.1016/0161-5890(95)00149-2.
Calreticulin is a new human rheumatic disease-associated autoantigen that plays a multifaceted role in cell biology. In earlier studies, this protein was shown to share an intimate relationship with the Ro/SS-A autoantigen complex, although the nature of this association continues to be debated. Since modulation of the Ro/SS-A autoantigen in epidermal keratinocytes has been implicated in the pathogenesis of subacute cutaneous lupus erythematosus and neonatal lupus erythematosus, we have begun to examine the transcriptional regulation of calreticulin. A 504 bp calreticulin promoter fragment was subcloned into a reporter gene plasmid containing firefly luciferase. Calcium ionophore, heat shock, and heavy metals such as zinc and cadmium were consistently found to increase calreticulin transcriptional activities in A431 cells (a human epidermoid squamous carcinoma cell line) under transient transfection conditions. These studies suggest that (a) calreticulin is regulated at the transcriptional level, and (b) calreticulin, like some other LE-related autoantigens, appears to function as a heat shock/stress-response gene.
钙网蛋白是一种新的与人类风湿性疾病相关的自身抗原，在细胞生物学中发挥多方面作用。在早期研究中，该蛋白被证明与Ro/SS - A自身抗原复合物关系密切，尽管这种关联的本质仍存在争议。由于表皮角质形成细胞中Ro/SS - A自身抗原的调节与亚急性皮肤型红斑狼疮和新生儿红斑狼疮的发病机制有关，我们已开始研究钙网蛋白的转录调控。将一个504 bp的钙网蛋白启动子片段亚克隆到含有萤火虫荧光素酶的报告基因质粒中。在瞬时转染条件下，持续发现钙离子载体、热休克以及锌和镉等重金属可增加A431细胞（一种人表皮样鳞状癌细胞系）中钙网蛋白的转录活性。这些研究表明：（a）钙网蛋白在转录水平受到调控；（b）钙网蛋白与其他一些与红斑狼疮相关的自身抗原一样，似乎作为一种热休克/应激反应基因发挥作用。
