Charité - Universitätsmedizin Berlin, Department of Dermatology and Allergy, Skin Cancer Center Charité, Berlin, Germany.
Curr Genomics. 2008 Sep;9(6):409-19. doi: 10.2174/138920208785699571.
Bcl-2 proteins are critical regulators of mitochondrial membrane permeability and the proapoptotic mitochondrial pathway. The family encloses pro- and antiapoptotic factors encoded by over 15 genes, which frequently give rise to alternative splice products. Antiapoptotic, proapoptotic multidomain, and proapoptotic BH3-only proteins are characterized by the presence of at least one of four Bcl-2 homology domains (BH 1-4). Their expression and activities are controlled by survival pathways as MAP kinases and protein kinase B/Akt, which are in touch with a number of transcription factors. In melanoma, the mitochondrial apoptosis pathways and Bcl-2 proteins appear of particular importance for apoptosis resistance, which has been addressed in clinical trials applying antisense-Bcl-2. Overexpression or induction of proapoptotic Bcl-2 proteins as well as the use of small molecule mimetics for the proapoptotic BH3 domain are further promising strategies.
Bcl-2 蛋白是线粒体膜通透性和促凋亡线粒体途径的关键调节因子。该家族包含由超过 15 个基因编码的促凋亡和抗凋亡因子，它们经常产生选择性剪接产物。抗凋亡、促凋亡多结构域和促凋亡 BH3 仅蛋白的特征是至少存在四个 Bcl-2 同源结构域 (BH1-4) 之一。它们的表达和活性受生存途径如 MAP 激酶和蛋白激酶 B/Akt 的控制，这些途径与许多转录因子有关。在黑色素瘤中，线粒体凋亡途径和 Bcl-2 蛋白对于抗凋亡似乎特别重要，这在应用反义-Bcl-2 的临床试验中已经得到了证实。Bcl-2 蛋白的过表达或诱导以及促凋亡 BH3 结构域的小分子模拟物的使用也是有前途的策略。
