MCL1
小结
MCL1编码蛋白（髓细胞白血病1）是一种抗凋亡蛋白，是BCL2促生存蛋白家族的成员。BCL2家族是由BCL2同源性（BH）结构域的存在来定义。MCL1类似于BCL2，是通过抑制细胞凋亡而赋予细胞存活。MCL1与BCL2共同调节线粒体外膜通透性，释放促凋亡因子如细胞色素C和激活半胱天冬酶。在许多实体瘤中发现MCL1基因拷贝数增加。10%以上的癌症中可观察到MCL1的扩增，在肺癌和乳腺癌中更高。MCL1的表达可以促进淋巴瘤的发生，是肺腺癌形成所必需的。通过抑制细胞凋亡，MCL1导致癌细胞存活率增加和对促凋亡刺激的产生抗性。
MCL1, an anti-apoptotic protein, is amplified in various cancer types.MCL1 (Myeloid cell leukemia 1) is a member of the BCL2 pro-survival protein family. The BCL2 family is defined by the presence of Bcl2 homology (BH) domains. MCL1, similar to BCL2, confers cell survival through inhibition of apoptosis. Together with BCL2, MCL1 regulates mitochondrial outer membrane permeabilization, release of pro-apoptotic factors such as cytochrome c and activation of caspases. Genome-wide studies have identified increased gene copy numbers of MCL1 across many cancer entities. Focal amplifications of MCL1 were found in over 10% of cancers and were even higher in lung and breast cancers. MCL1 expression can drive lymphomagenesis and is required for lung adenocarcinoma formation. Through inhibition of apoptosis, MCL1 leads to increased survival of cancer cells and resistance to pro-apoptotic stimuli. Therapies targeting MCL1 and other BCL2 family members are being developed and are currently under investigation.