Brn-3a, a neuronal transcription factor of the POU gene family: indications for its involvement in cancer and angiogenesis.
Brn-3a, a member of the POU gene family (so-called because of the similarity with the group of transcription factors Pit, Oct, and Unc), was found in neuronal cells engaged in the transcription activity of the p1 and p2 promoters of the most powerful antiapoptotic gene, namely, Bcl-2. The alternative splicing of Brn-3a mRNA produces two molecular forms: a longer, Bcl-2 transactivating form, and a shorter inactive form, lacking 84 AA in the aminoterminus. In neuronal cells, following Brn-3a gene transfection and superexpression, an increase of 30 fold of the Bcl-2 protein occurs, leading to apoptosis protection. However, recent works demonstrate that Brn-3a expression is not restricted to neuronal cells, as its activity was detected also in cancer cells of non-neuronal nature. Looking for mechanisms linking Brn-3a to carcinogenesis, we discuss the role of this transcription factor in influencing Bcl-2/p53 antagonism and Bcl-2/VEGF induction of tumor angiogenesis, concluding this review with a proposal for the oncogenic nature of Brn-3a.
Chiarugi
Vincenzo
V
Operative Unit of Molecular Biology of Azienda Ospedaliera Careggi, Italy.
Del Rosso
Mario
M
Magnelli
Lucia
L
D017398:Alternative Splicing; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009857:Oncogenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53