The N-terminal domain unique to the long form of the Brn-3a transcription factor is essential to protect neuronal cells from apoptosis and for the activation of Bbcl-2 gene expression.
The ability of the POU family transcription factor Brn-3a to stimulate neurite outgrowth and the expression of the genes encoding neuronal proteins such as the neurofilaments and SNAP-25 has previously been shown to be dependent upon the C-terminal POU domain which can mediate both DNA binding and transcriptional activation. We show here, however, that the ability of Brn-3a to activate Bcl-2 expression and protect neuronal cells from apoptosis (programmed cell death) requires a distinct N-terminal activation domain. Bcl-2 gene activation and protection from apoptosis are thus produced only by the long form of Brn-3a which contains this domain and not by a naturally occurring short form lacking this domain or by the isolated POU domain, although all these forms of Brn-3a can stimulate neurite outgrowth. Hence Brn-3a is a multi-functional transcription factor with different regions of the factor mediating its different effects and two distinct forms with different properties being generated by alternative splicing.
Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London,Cleveland Street, London W1P 6DB, UK and Department of Medicine, Stanford University Medical Center, Stanford, CA 94305-5112, USA.
M D
MD
Smith
S J
SJ
Dawson
L M
LM
Boxer
D S
DS
Latchman
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006801:Humans; D007700:Kinetics; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors