Transcriptional activator; Plays an important role in the control of proliferation and differentiation of hematopoietic progenitor cells.
ohne Gefährdungspotential
c-Myb overexpression and dysregulation have been frequently observed in hematopoietic tumors, particularly AML, ALL, and lymphomas. Seven well-known transcript variants and isoforms of c-Myb have been reported. In soft agar assays using NIH3T3 cells engineered to overexpress various c-Myb isoforms, c-Myb-9A exhibited the strongest colony formation activity, whereas WT-c-Myb did not exhibit significant transforming activity. c-Myb-9A, which lacks a C-terminal negative regulatory domain (NRD) and is structurally similar to the v-Myb AMV oncoprotein, is known to exhibit a significantly higher transactivation capacity relative to that of WT-c-Myb. C-terminal deletion mutants of c-Myb led to significant increases in DNA-binding activity, transactivation, and transformation activity, indicating the importance of the NRD in the negative self-regulation of c-Myb.
AMV-like virus expressing authentic c-Myb did not transform avian bone marrow cells. However, truncation of either the N or C terminus of c-Myb was sufficient to activate the transforming potential of this protein.
To assess the full spectrum of Myb's oncogenic capability, a replication-competent retroviral vector (RCAMV) was used to express a full-length protein, an amino-terminally truncated protein, a carboxyl-terminally truncated protein (T-Myb), or a doubly truncated protein in vivo. These viruses were injected intravenously into 10-day chicken embryos, and the infected chicks were monitored for tumors. Approximately 4 to 8 weeks after hatching, the majority (30 of 39 [77%]) of animals infected with the T-Myb retrovirus (without 214 carboxyl-terminal residues) developed nodular muscle tumors which could be identified as fibrosarcomas. In comparison, no sarcomas were observed in any of the animals infected with the amino-terminally truncated or doubly truncated viruses. A loss of carboxyl-terminal but not amino-terminal sequences can thus convert Myb into a potent in vivo transforming protein for nonhematopoietic mesenchymal cells. In comparison, a truncation of either or both ends of the protein can activate Myb into a hematopoietic cell-transforming protein.
Die ursächliche Beteiligung des nicht verkürzten Proteins an der Entstehung von Tumoren ist nicht gezeigt.
Nakano K et al., Clin Cancer Res. 2016;22(23):5915-5928.
Grässer FA et al., Mol Cell Biol. 1991;11(8):3987-3996.
Press RD et al., Mol Cell Biol. 1994;14(4):2278-2290.
