Neurotrophin p75 receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis: implications for diabetes-induced impaired neovascularization in ischemic limb muscles.

Diabetes impairs endothelial function and reparative neovascularization. The p75 receptor of neurotrophins (p75(NTR)), which is scarcely present in healthy endothelial cells (ECs), becomes strongly expressed by capillary ECs after induction of peripheral ischemia in type-1 diabetic mice. Here, we show that gene transfer-induced p75(NTR) expression impairs the survival, proliferation, migration, and adhesion capacities of cultured ECs and endothelial progenitor cells (EPCs) and inhibits angiogenesis in vitro.

p38MAPK delta controls c-Myb degradation in response to stress.

The c-myb gene is the progenitor of the v-myb oncogene, which causes avian myelomonocytic leukemia. Dysregulated c-myb gene expression is linked to the development of myeloid leukemia in mice and is predictive of poor prognosis in human colorectal cancer. Among the variety of post-translational modifications controlling the c-Myb protein, phosphorylation was shown to affect the transactivation activity and the rate of protein degradation.

Mismatch repair status and the response of human cells to cisplatin.

The emergence of resistance to cisplatin is a serious drawback of cancer therapy. To help elucidate the molecular basis of this resistance, we examined matched ovarian cancer cell lines that differ in their DNA mismatch repair (MMR) status and the response to cisplatin. Checkpoint activation by cisplatin was identical in both lines.

Enhanced proliferative potential of hematopoietic cells expressing degradation-resistant c-Myb mutants.

The c-myb gene encodes a transcription factor required for proliferation, differentiation, and survival of hematopoietic cells. Expression of c-Myb is often increased in hematological malignancies, but the underlying mechanisms are poorly understood. We show here that c-Myb has a longer half-life (at least 2-fold) in BCR/ABL-expressing than in normal hematopoietic cells.