No abstract

Type A behaviour pattern and acute life stress affect the development and spontaneous conversion of atrial fibrillation. Patients with acute stress showed the highest probability of spontaneous conversion followed by patients with Type A behaviour. Other socio-economic factors affect spontaneous conversion and recurrences of lone atrial fibrillation to a lesser extent.

The DNA binding activity of FUS (also known as TLS), a nuclear pro-oncogene involved in multiple translocations, is regulated by BCR-ABL in a protein kinase C␤II (PKC␤II)-dependent manner. We show here that in normal myeloid progenitor cells FUS, although not visibly ubiquitinated, undergoes proteasomedependent degradation, whereas in BCR-ABL-expressing cells, degradation is suppressed by PKC␤II phosphorylation. Replacement of serine 256 with the phosphomimetic aspartic acid prevents proteasome-dependent proteolysis of FUS, while the serine-256-to-alanine FUS mutant is unstable and susceptible to degradation. Ectopic expression of the phosphomimetic S256D FUS mutant in granulocyte colony-stimulating factor-treated 32Dcl3 cells induces massive apoptosis and inhibits the differentiation of the cells escaping cell death, while the degradation-prone S256A mutant has no effect on either survival or differentiation. FUS proteolysis is induced by c-Jun, is suppressed by BCR-ABL or Jun kinase 1, and does not depend on c-Jun transactivation potential, ubiquitination, or its interaction with Jun kinase 1. In addition, c-Jun-induced FUS proteasome-dependent degradation is enhanced by heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and depends on the formation of a FUS-Jun-hnRNP A1-containing complex and on lack of PKC␤II phosphorylation at serine 256 but not on FUS ubiquitination. Thus, novel mechanisms appear to be involved in the degradation of FUS in normal myeloid cells; moreover, the ability of the BCR-ABL oncoprotein to suppress FUS degradation by the induction of posttranslational modifications might contribute to the phenotype of BCR-ABL-expressing hematopoietic cells.FUS, also known as TLS or heterogeneous nuclear ribonucleoprotein (hnRNP) P2, was first discovered as the N-terminal part of a fusion with CHOP in myxoid liposarcoma carrying the t(12;16) translocation (8, 33) and was subsequently detected in different types of human myeloid leukemia (37), in which the C terminus of FUS is replaced by the DNA-binding domain of ERG (28). The C terminus of FUS is required for binding to pre-mRNA and mRNA, while the N terminus appears to function as a transcription activation domain (34).

No abstract