Molecular Mechanisms Associated with the Regulation of Apoptosis by the Two Alternatively Spliced Products of c-Myb

AUTOR(ES)

Kumar, Atul

FONTE

American Society for Microbiology

RESUMO

The c-myb proto-oncogene encodes two alternatively spliced mRNAs, which in turn code for proteins of 75 kDa and 89 kDa. It is at present unclear whether the two isoforms of c-Myb perform identical functions or whether they mediate different biological effects. To assess their role in apoptotic death of hematopoietic cells, we expressed the two isoforms of c-Myb in the murine myeloid cell lines 32Dcl3 and FDCP1. Our results show that while ectopic overexpression of p75 c-Myb results in the acceleration of cell death, similar overexpression of p89 c-Myb results in the protection of cells from apoptotic death. An analysis of gene expression changes with mouse cDNA expression arrays revealed that while p75 c-Myb blocked the expression of glutathione S-transferase μ mRNA, p89 c-Myb greatly enhanced the expression of this gene. These results were further confirmed by Northern blot analysis. Ectopic overexpression of the glutathione S-transferase μ gene in 32Dcl3 cells resulted in protection of cells from interleukin-3 withdrawal-induced cell death similar to that seen with the ectopic overexpression of p89 c-Myb. These results suggest that the two isoforms of c-Myb differentially regulate apoptotic death of myeloid cells through differential regulation of glutathione S-transferase μ gene expression.

Documentos Relacionados

• Overexpression of an Alternatively Spliced Form of c-Myb Results in Increases in Transactivation and Transforms Avian Myelomonoblasts
• A second c-myb protein is translated from an alternatively spliced mRNA expressed from normal and 5'-disrupted myb loci.
• Mechanism of c-myc regulation by c-Myb in different cell lineages.
• Trans-activation by the c-myb proto-oncogene.
• A potential splicing factor is encoded by the opposite strand of the trans-spliced c-myb exon.