Fra A M, Pasqualetto E, Mancini M, Sitia R
DIBIT-San Raffaele Scientific Institute, 20132, Milan, Italy.
Gene. 2000 Feb 8;243(1-2):75-83. doi: 10.1016/s0378-1119(99)00559-4.
Caveolin-1 and caveolin-2 are related proteins involved in the biogenesis of caveolae. The corresponding genes in humans (CAV and CAV2, respectively), have been mapped to a common locus in chromosome 7q31.1, and are possible candidates for the tumor suppressor gene postulated in this region. Here, we show that CAV and CAV2 are independent transcriptional units lying in the same orientation, with CAV2 centromeric and about 17kb upstream to CAV. The two genes have similar tissue expression patterns. Alternative termination/polyadenylation generates two CAV2 mRNAs. Multiple transcriptional start sites spanning 35bp upstream from the CAV2 ATG are detected by 5' RACE, consistent with a TATA-less promoter predicted by sequence analysis. The CAV2 promoter region contains two SRE-like boxes resembling those described in the CAV promoter and proposed to link transcription to intracellular cholesterol levels. However, exogenous sterols had only minor effects on CAV and CAV2 RNA levels in HeLa cells, suggesting that SREBPs are not sufficient to regulate caveolin transcription.
小窝蛋白-1和小窝蛋白-2是参与小窝生物发生的相关蛋白。人类中的相应基因（分别为CAV和CAV2）已被定位到7号染色体q31.1的一个共同位点，并且可能是该区域中假定的肿瘤抑制基因的候选基因。在这里，我们表明CAV和CAV2是位于相同方向的独立转录单元，CAV2位于着丝粒侧，且在CAV上游约17kb处。这两个基因具有相似的组织表达模式。可变终止/多聚腺苷酸化产生两种CAV2 mRNA。通过5'RACE检测到多个转录起始位点，跨越CAV2 ATG上游35bp，这与序列分析预测的无TATA启动子一致。CAV2启动子区域包含两个类似于CAV启动子中描述的SRE样框，并被认为将转录与细胞内胆固醇水平联系起来。然而，外源性固醇对HeLa细胞中CAV和CAV2 RNA水平只有轻微影响，这表明SREBP不足以调节小窝蛋白的转录。
