Brancaccio Mara, Rocca Stefania, Seclì Laura, Busso Elena, Fusella Federica
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Oncotarget. 2015 Dec 15;6(40):42603-12. doi: 10.18632/oncotarget.6058.
Morgana is a chaperone protein able to bind to ROCK I and II and to inhibit their kinase activity. Rho kinases are multifunctional proteins involved in different cellular processes, including cytoskeleton organization, centrosome duplication, cell survival and proliferation. In human cancer samples Morgana appears to be either downregulated or overexpressed, and experimental evidence indicate that Morgana behaves both as an oncosuppressor and as a proto-oncogene. Our most recent findings demonstrated that if on the one hand low Morgana expression levels, by inducing ROCK II hyperactivation, cause centrosome overduplication and genomic instability, on the other hand, Morgana overexpression induces tumor cell survival and chemoresistance through the ROCK I-PTEN-AKT axis. Therefore, Morgana belongs to a new class of proteins, displaying both oncogenic and oncosuppressor features, depending on the specific cellular context.
莫尔加娜是一种伴侣蛋白，能够与ROCK I和ROCK II结合并抑制它们的激酶活性。Rho激酶是多功能蛋白，参与不同的细胞过程，包括细胞骨架组织、中心体复制、细胞存活和增殖。在人类癌症样本中，莫尔加娜似乎要么下调要么过表达，实验证据表明莫尔加娜既表现为肿瘤抑制基因，又表现为原癌基因。我们最近的研究结果表明，一方面，低水平的莫尔加娜表达通过诱导ROCK II过度激活，导致中心体过度复制和基因组不稳定；另一方面，莫尔加娜过表达通过ROCK I-PTEN-AKT轴诱导肿瘤细胞存活和化疗耐药性。因此，莫尔加娜属于一类新的蛋白质，根据特定的细胞环境，既表现出致癌特征，又表现出肿瘤抑制特征。
