Nuclear localization of v-Abl leads to complex formation with cyclic AMP response element (CRE)-binding protein and transactivation through CRE motifs.
Deregulated expression of v-abl and BCR/abl genes has been associated with myeloproliferative syndromes and myelodysplasia, both of which can progress to acute leukemia. These studies identify the localization of the oncogenic form of the abl gene product encoded by the Abelson murine leukemia virus in the nuclei of myeloid cells and the association of the v-Abl protein with the transcriptional regulator cyclic AMP response element-binding protein (CREB). We have mapped the specific domains within each of the proteins responsible for this interaction. We have shown that complex formation is a prerequisite for transcriptional potentiation of CREB. Transient overexpression of the homologous cellular protein c-Abl also results in the activation of promoters containing an intact CRE. These observations identify a novel function for v-Abl, that of a transcriptional activator that physically interacts with a transcription factor.
Birchenall-Roberts
M C
MC
Biological Carcinogenesis and Development Program, Science Applications International Corporation Frederick, Maryland.
Ruscetti
F W
FW
Kasper
J J
JJ
Bertolette
D C
DC
Yoo
Y D
YD
Bang
O S
OS
Roberts
M S
MS
Turley
J M
JM
Ferris
D K
DK
Kim
S J
SJ
D001483:Base Sequence; D001665:Binding Sites; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D015533:Transcriptional Activation
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D009838:Oligodeoxyribonucleotides; D016374:Oncogene Proteins v-abl; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors