MED12
小结
MED12是致癌基因，编码蛋白是参与转录起始的CDK8亚复合物的组分，MED12蛋白是激活CDK8激酶的关键。包括MED13、CDK8激酶和细胞周期蛋白C的CDK8亚复合物可以调节中介物-聚合酶II的相互作用，从而调节转录起始和重新起始率。MED12中最常见的突变位于2号外显子。在子宫平滑肌瘤、乳腺纤维腺瘤和乳腺叶状肿瘤中已经检测到该区域的变异。在良性乳腺肿瘤中，MED12热点突变被认为是导致雌激素信号失调的早期事件。MED12是子宫肌瘤中最常见的突变基因，表明它在这些病变的发生中起主要作用。在子宫平滑肌肉瘤，结直肠癌，前列腺癌都检测到MED12的突变，这些突变通过扰乱与p53和雄激素信号传导相关的转录程序在肿瘤发生中起作用。
MED12 is a component of CDK8, a subcomplex involved in transcription initiation. MED12 plays a role in the genesis of benign tumors such as uterine leiomyoma and breast fibroadenoma and is altered in a variety of estrogen-dependent tumors.MED12 is a component of the CDK8 subcomplex that is involved in transcription initiation. The MED12 protein is essential for activating CDK8 kinase. The CDK8 subcomplex which includes MED13, CDK8 kinase and cyclin C, modulates mediator-polymerase II interactions thereby regulating transcription initiation and reinitiation rates. The most commonly seen mutations in MED12 are in exon 2. Mutations in this domain have been described in uterine leiomyomas, breast fibroadenomas, and Phyllodes tumors of the breast. In benign breast tumors, MED12 hotspot mutations are thought to be early events that lead to deregulation of estrogen signaling. MED12 is the most frequently mutated gene in uterine leiomyomas, suggesting it has a major role in the development of these lesions. MED12 somatic exon 2 mutations have also been described in uterine leiomyosarcoma (uLMS) and colorectal cancer (CRC). The presence of the same MED12 mutations in uLMS as in uterine leiomyomas suggests that a subgroup of the malignant tumors may develop from a leiomyoma precursor. Leucine (L) to Phenylalanine (F) mutations at amino acid 1224 have been described in prostate cancer. These mutations are thought to play a role in tumorigenesis via perturbation of transcriptional programs linked to p53 and androgen signaling.