Cloning and characterization of the 5'UTR of the rat anti-apoptotic Bcl-w gene.
The anti-apoptotic Bcl-w regulator, which is expressed in the developing and mature brain, not only promotes neuronal survival, but also neuronal differentiation. However, its transcriptional regulation remains to be elucidated due to a lack of knowledge of the Bcl-w promoter. Here, we report the mapping and characterization of the rat Bcl-w promoter, which is highly conserved between the human, mouse, and rat species. Using a series of 5' and 3' deletions, we mapped the TATA-less minimal Bcl-w promoter and showed that it is under a combinatorial regulation with the neurogenic bHLH transcription factor NeuroD6 mediating its activation, validating our previous finding of increased expression of the Bcl-w protein in stably transfected PC12-NeuroD6 cells. Upon stress, NeuroD6 promotes colocalization of Bcl-w with mitochondria and endoplasmic reticulum. Finally, we provide the first evidence of Bcl-w localization in the growth cones of differentiating neuronal cells, suggestive of a potential synaptic neuroprotective role.
Uittenbogaard
Martine
M
Department of Anatomy and Regenerative Biology, George Washington University Medical Center, 2300 I Street N.W., Washington, DC 20037, USA.
Baxter
Kristin Kathleen
KK
Chiaramello
Anne
A
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; C491072:Bcl2l2 protein, rat; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2