NUCLEAR-LOCALIZATION OF V-ABL LEADS TO COMPLEX-FORMATION WITH CYCLIC-AMP RESPONSE ELEMENT (CRE)-BINDING PROTEIN AND TRANSACTIVATION THROUGHCRE MOTIFS

Deregulated expression of v-abl and BCR/abl genes has been associated with myeloproliferative syndromes and myelodysplasia, both of which ca n progress to acute leukemia. These studies identify the localization of the oncogenic form of the abl gene product encoded by the Abelson m urine leukemia virus in the nuclei of myeloid cells and the associatio n of the v-Abl protein with the transcriptional regulator cyclic AMP r esponse element-binding protein (CREB). We have mapped the specific do mains within each of the proteins responsible for this interaction. We have shown that complex formation is a prerequisite for transcription al potentiation of CREB. Transient overexpression of the homologous ce llular protein c-Abl also results in the activation of promoters conta ining an intact CRE. These observations identify a novel function for v-Abl, that of a transcriptional activator that physically interacts w ith a transcription factor.