Poly(ADP-ribose) polymerase is a B-MYB coactivator.
B-MYB is implicated in cell growth control, differentiation, and cancer and belongs to the MYB family of nuclear transcription factors. Evidence exists that cellular proteins bind directly to B-MYB, and it has been hypothesized that B-MYB transcriptional activity may be modulated by specific cofactors. In an attempt to isolate proteins that interact with the B-MYB DNA-binding domain, a modular domain that has the potential to mediate protein-protein interaction, we performed pull-down experiments with a glutathione S-transferase-B-MYB protein and mammalian protein extracts. We isolated a 110-kDa protein associated endogenously with B-MYB in the nuclei of HL60 cells. Microsequence analysis and immunoprecipitation experiments determined that the bound protein was poly(ADP-ribose) polymerase (PARP). Transient transfection assays showed that PARP enhanced B-MYB transactivation and that PARP enzymatic activity is not required for B-MYB-dependent transactivation. These results suggest that PARP, as a transcriptional cofactor of a potentially oncogenic protein, may play a role in growth control and cancer.
Cervellera
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MN
Department of Molecular Pharmacology and Pathology, Consorzio Mario Negri Sud, S. Maria Imbaro, via Nazionale, 66030 Chieti, Italy.
Sala
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A
D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D005982:Glutathione Transferase; D018922:HL-60 Cells; D006801:Humans; D008322:Mammals; D015513:Oncogene Proteins / Q000378:metabolism; D012516:Osteosarcoma; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase