Abstract
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.
Highlights
Morgana is a protein containing two CHORD domains able to coordinate Zn++ ions and a C-terminal CS domain [1], homologous to the small chaperones α-crystallin and p23 (Figure 1) [2]
When we analyzed bone marrow biopsies from 5 patients affected by atypical” CML (aCML), we found low/indetectable Morgana expression levels and high ROCK activity in all cases
Low Morgana expression levels can be the driving cause of human aCML, but our work highlighted that Morgana downregulation cooperates with the BCR/ ABL oncogene in the 16% of chronic myeloid leukemia (CML) Philadelphia chromosome (Ph) positive (Ph+) patients
Summary
Morgana is a protein containing two CHORD (cysteine and histidine rich) domains able to coordinate Zn++ ions and a C-terminal CS (after CHORD-containing proteins and Sgt1) domain [1], homologous to the small chaperones α-crystallin and p23 (Figure 1) [2]. In morgana +/- cells a higher amount of NPM binds to ROCK II, causing its hyperactivity and leading to centrosome overduplication [14]. When we analyzed bone marrow biopsies from 5 patients affected by aCML, we found low/indetectable Morgana expression levels and high ROCK activity in all cases.
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