RGD Reference Report - Transcription factor SCIRR69 involved in the activation of brain-derived neurotrophic factor gene promoter II in mechanically injured neurons. - Rat Genome Database

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Transcription factor SCIRR69 involved in the activation of brain-derived neurotrophic factor gene promoter II in mechanically injured neurons.

Authors: Liu, Yong  Que, Haiping  Ma, Zhenlian  Yang, Shuguang  Ni, Yanli  Luo, Zhanpeng  Tang, Ning  Yang, Jingwen  Jing, Shuqian  Liu, Shaojun 
Citation: Liu Y, etal., Neuromolecular Med. 2013 Sep;15(3):605-22. doi: 10.1007/s12017-013-8245-y. Epub 2013 Jul 11.
RGD ID: 13515084
Pubmed: PMID:23842743   (View Abstract at PubMed)
DOI: DOI:10.1007/s12017-013-8245-y   (Journal Full-text)

The spinal cord injury and regeneration-related gene #69 (SCIRR69), which was identified in our screen for genes upregulated after spinal cord injury, encode a protein belonging to the cAMP response element-binding protein (CREB)/ATF family of transcription factors. Our previous study showed that SCIRR69 functions as a transcriptional activator. However, the target gene regulated by SCIRR69 and its roles in injured neurons remain unknown. In this study, we showed that SCIRR69 is widely distributed in the central nervous system. Full-length SCIRR69 is an endoplasmic reticulum-bound protein. Following mechanical injury to neurons, SCIRR69 was induced and proteolytically cleaved by site-1 and site-2 proteases, and the proteolytically cleaved SCIRR69 (p60-SCIRR69) was translocated to the nucleus where it bound to brain-derived neurotrophic factor (BDNF) gene promoter II. In addition, loss- and gain-of-function studies confirmed that SCIRR69 is involved in the regulation of BDNF expression in injured neurons. As expected, the culture supernatants of PC12 cells stably expressing p60-SCIRR69 contained higher levels of BDNF, and more remarkably promoted neurite outgrowth in a spinal cord slice culture model in vitro than the supernatants of control cells. These results suggest that SCIRR69 is a novel regulator of the BDNF gene and may play an important role in the repair and/or regeneration of damaged neural tissues by specifically activating BDNF promoter II.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Creb3l2Ratpositive regulation of gene expression  IDA  RGD 
Creb3l2Ratpositive regulation of neuron projection development  IDA  RGD 

Cellular Component

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Creb3l2Ratchromatin  IDA  RGD 
Creb3l2Ratperinuclear endoplasmic reticulum  IDA  RGD 

Molecular Function

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Creb3l2RatDNA-binding transcription activator activity, RNA polymerase II-specific  IDA  RGD 


Genes (Rattus norvegicus)
Creb3l2  (cAMP responsive element binding protein 3-like 2)