Smith M D, Dawson S J, Boxer L M, Latchman D S
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.
Nucleic Acids Res. 1998 Sep 15;26(18):4100-7. doi: 10.1093/nar/26.18.4100.
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.
此前已表明，POU家族转录因子Brn-3a刺激神经突生长以及编码神经元蛋白（如神经丝和SNAP-25）的基因表达的能力取决于C端POU结构域，该结构域可介导DNA结合和转录激活。然而，我们在此表明，Brn-3a激活Bcl-2表达并保护神经元细胞免受凋亡（程序性细胞死亡）的能力需要一个独特的N端激活结构域。因此，只有包含该结构域的Brn-3a长形式才能产生Bcl-2基因激活和抗凋亡作用，而缺乏该结构域的天然短形式或分离的POU结构域则不能，尽管所有这些形式的Brn-3a都能刺激神经突生长。因此，Brn-3a是一种多功能转录因子，其不同区域介导不同效应，通过可变剪接产生具有不同特性的两种不同形式。
